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TGFB1 activates SMAD2. 242 / 310
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"It is now well accepted that upon binding to its receptor, TGF-β1 activates two downstream proteins, Smad2 and Smad3, to exert its biological effects, which are negatively regulated by Smad7, a downstream inhibitory Smad in TGF-β signaling xref ."
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"Studies by Ohnishi and co-workers revealed that TGF-beta1 stimulated PSC activation (indicated by increased alpha-SMA expression) in a Smad2 dependent manner, while Smad3 was required for TGF-beta1-induced growth inhibition [XREF_BIBR]."
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"Finally, after transient knockdown of TRAIL-R1 in Panc1 cells there was a tendency towards enhanced activation of Smad2 and JNK1/2 signalling by exogenous TGFbeta1."
30366420
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"Activated PSCs secrete TGFbeta1 that activates smad2 signaling in cancer cells and induces cell stemness and drug resistance ."
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": After AK and topical application of TGF-beta1, moesin was the most highly upregulated gene among 84 cytoskeleton regulator genes; iontophoresing moesin siRNA into the corneal stroma reduced the expression of alpha-SMA to 0.22-, 0.52-, and 0.31-fold of control at postoperative (PO) day 1, 3, and 5, respectively; also, upregulation of phospho-Smad 2 induced by TGF-beta1 was reduced by moesin siRNA to 0.59-, 0.56-, and 0.31-fold of control and expression of phospho-Smad 3 was reduced to 0.58-, 0.53-, and 0.47-fold of control at the same PO days."
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"However, in our current study, PD98059 and SB203580 failed to prevent TGF-β1–induced Smad2 activation, and Smad2 siRNA failed to prevent TGF-β1–induced ERK and P38 MAPK activation which demonstrated that there were no crosstalk between Smad2 and MAPK signals in ADPKD cyst-lining epithelial cells."
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"As Fig. 4 shows, TGF-beta 1 was able to activate Smad2 in parental as well as in Smad4wt-2 Car C cells with different kinetics."
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"Protein tyrosine phosphatase 1B regulates TGF beta 1 induced Smad2 activation through PI3 kinase dependent pathway."
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"27 The early studies have shown that km23- 1, a TGF-beta receptor binding protein, serves as a critical adaptor coupling activation of the receptor to the Ras effector pathway required for autoregulation of TGF-beta1 production independent of Smad2."
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"Mechanism study indicated that NLE markedly suppressed TGF-β1-induced Smad2 and Smad3 activation and nuclear translocation."
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"TGF-beta1 is known to activate SMAD-2 and SMAD-3; however, the pro fibrotic effects of TGF-beta1 signaling have been largely attributed to SMAD-3 mediated signaling."
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"In an NEC animal model, oral administration of the isoform TGF-β1 activated the downstream effector Smad2 in intestine and significantly reduced NEC incidence."
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"However, this counter balancing mechanism is also altered because TGF-beta1 induces Smurf2, a ubiquitin E3-ligase, to target Smad7 as well as Smad2 for degradation."
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"Also, TGF-beta1 activated SMAD2 and SMAD1/5, an effect that was abolished by ALK5 inhibition."
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"A human keratinocyte-fibroblast co-culture model was established to investigate the protein levels of human collagen type-I, III and V in a western blotting analysis, the secreted transforming growth factor-beta1 (TGF-beta1) in an enzyme linked immunosorbent assay (ELISA) and the mRNA levels of TGF-beta1 's intracellular signaling molecules (SMAD2, 3, 4 and 7) in a real-time PCR analysis."
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"23 Analysis of Smad1 and Smad2 C-terminal phosphorylation showed that TGFbeta1 induced P-Smad2, but not P-Smad1."
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"Smad2 and Smad3 are mainly activated by TGF- β and the activin receptors T β RI and ActRIB, while Smad1, Smad5, and Smad8 are primarily activated by ALK-1, ALK-2, BMP-RIA/ALK-3, BMP-RIB/ALK-6, and other ligands."
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"Our results demonstrate that in PDV cells, TGF-beta1 greatly induces the activation of both Smad2 and Smad3."
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"The objective of this study was to determine the effect of Smad2 in peritoneal fibrosis, induced by TGF-beta1, on dissemination of gastric cancer."
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"LY2109761 inhibits TGF-β1–induced Smad2 activation in PC-3 cells and PMOs."
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"Mechanistic studies found that Smad2 phophorylation and Snail expression were markedly increased in PTECs treated with TGF-beta1, whereas the CaSR CRISPR activation plasmid and cinacalcet substantially suppressed this induction."
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"Rk1 and Rg5 inhibit TGF-β1-activation of Smad2 and Smad3."
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"These results indicated that calcium signaling might regulate EMT induced by TGF-beta1 in lung cancer cells.To explore whether BAPTA-AM suppress EMT by modulating Smad signaling, the phosphorylation o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In conclusion, it was demonstrated that SP1 promoted TGF-beta1 expression, activated the SMAD2 pathway and induced VEGF secretion, which may enhance angiogenic processes in preosteoblasts."
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"TGF-beta1 exposure activated Smad2 and Smad3 as evidenced by their phosphorylation within minutes of TGF-beta1 exposure (XREF_FIG)."
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"Likewise, PP2 and PP1 but not SU6656 effectively blocked TGF-β1-induced activation of Smad2 and p38 MAPK and partially suppressed Smad activation and transcriptional activity on TGF-β/Smad-responsive reporters of a kinase-active TβRI mutant ectopically expressed in Panc1 cells."
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"In summary, this study clearly shows that the TGFbeta1 induced Smad2 nuclear translocation is negatively regulated by intracellular Ca (2+) in OLI-neu cells and that increased intracellular Ca (2+) concentrations block Smad2 mediated transcription of TGFbeta target genes."
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"Additionally, NF-kappaB can also promote the expression of TGF-beta1 and activate TGF-beta1 and Smad2 signaling by binding with NF-kappaB combining site locating in TGF-beta1 activating factor-tissue transglutaminase (tTG) gene promoter [XREF_BIBR]."
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"TGF-β1 induced activations of Smad2 and miRNAs inhibit SF-1 and LRH-1 dependent CYP19 expression in rat Leydig cells †."
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"TGF-beta1 activates the canonical Smad-2 and -3 dependent pathways and the non canonical PI3K, MEK-1 MAPK, JNK and p38 dependent pathways through binding to its receptors TGF-beta-RI and TGF-beta-RII [XREF_BIBR]."
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"In conclusion, our data revealed the insulin inhibitory effects on TGFbeta1-induced Smad2 activation and the regulation role of PTP1B in the inhibition events."
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"It was also found that the phosphorylation level of Smad3 was slightly higher than that of Smad2 after treated with TGF-beta 1 for 0.5 to 2 h, whereas the phosphorylation level of Smad3 was slightly lower than that of Smad2 after treatment with TGF-beta 1 for 6 h (XREF_FIG and XREF_FIG), which suggested that Smad2 and Smad3 may play different roles when transmitting TGF-beta 1 signals in cells."
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"Consistently, pretreatment of smooth muscle cells in culture with IL-17A blunted the activation of Smad2 by TGFβ1."
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"Consistently, pretreatment of smooth muscle cells in culture with IL-17A blunted the activation of Smad2 by TGFbeta1."
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"In this report, by using the IN Cell Analyzer 1000, the fluorescence cell imaging instrument, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) could regulate TGFbeta1-induced Smad2 activation in a PI3 kinase-dependent manner."
16949833
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"Along with this switch, TGF-β1 activated its downstream effector SMAD2."
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"TGF-beta1 activates Smad2 and Smad3 as ' pathway specific Smads ' but not Smad1, Smad5 and Smad8 that are BMP pathway specific [10]."
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"TGF-beta1 activated the transcription factors, Smad2 and Smad3, by phosphorylation in a time dependent manner and elevated collagen I protein, one of the well-known extracellular matrix (ECM) proteins, in a dose dependent manner (data not shown)."
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"TGFβ1 could activate SMAD2 and SMAD3 in cancer cell which form complexes with transcriptional coactivators or cosuppressors to regulate gene expression [ xref ]."
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"Smad2, Smad3 and Smad4 are present and activated by TGF-beta1 in MDPC-23 cells."
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"TGF-beta1 induces peritoneal fibrosis by activating the Smad2 pathway in mesothelial cells and promotes peritoneal carcinomatosis."
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"The above data showed that TGF-β1-induced Smad2 and Smad3 activation was sensitive to dasatinib inhibition."
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"As shown in Fig. 4 A, the HOXB9 overexpression in BEL-7405 cells significantly increased the expression of TGF-beta1 and upregulated its downstream protein p-Smad2."
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"In addition, 4 h of 17β-estradiol and Fulvestrant treatment had similar inhibitory effect on TGF-β1-induced Smad2 activation and total Smad2 protein level."
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"These results suggested that miR-19a-3p/19b-3p can directly and negatively regulate TGF-beta R II gene expression and inhibit the TGF-beta and Smad2 signaling transduction activated by TGF-beta1."
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"For analysis of Smad2 and Smad3 activation by TGF-β1, these authors used a single concentration of 100 nM dasatinib rather than providing a dose–response curve with higher concentrations."
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"Biochemically, dnSrc inhibition failed to block TGF-beta1 and ALK5-induced activation of Smad2 and Smad3, but partially inhibited transcriptional activation of TGF-beta and Smad-responsive reporter genes, and effectively blocked basal and TGF-beta1-induced activation of p38 MAPK."
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"Moreover, they observed that over-expression of Smad 7 resulted in inhibi-tion of TGF-β1-induced Smad 2 activation with the prevention of EMT and collagen synthesis."
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"When compared with NSFs, the endogenous expression of Smad2 in HSFs was up-regulated and TGF-beta1 could further stimulate the production of Smad2."
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"Notably, TGF-beta1 was shown to target SMAD2 for degradation by the proteasomal machinery [XREF_BIBR]."
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"As expected, no FSP1 was expressed after TGF-beta1 stimulation in the Smad 2, Smad 3, or Smad 4 knocked down cells."
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"In explants, 1ng/ml TGFbeta1 induced pSmad2, but Smad1/5 phosphorylation was more difficult to detect, in contrast to in monolayer cultures."
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"TGFbeta1 induced activation of both Smad2 and extracellular signal regulated kinases (ERK1/2)."
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"Consistently, SMAD2 was activated by TGFβ1 and inhibited by GLT or upon combination with cisplatin ( xref )."
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"Because a number of cell-specific interactions have been described between TGF-beta1-driven Smad signaling and the c-Jun N-terminal kinase (JNK) pathway, we have investigated the effects of JNK inhibition on TGF-beta1 activation of Smad2, inhibition of branching, induction of CTGF expression, and apoptosis in mouse embryonic lung explants."
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"We previously demonstrated that TGF-beta1 induces Smad2 / 3 activation to increase pde4d expression , leading to increased cAMP hydrolysis and attenuating HASM cell relaxation responses ."
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"TGF-beta1 treatment resulted in activation of Smad2 as demonstrated by increased phosphorylated Smad2."
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"TGF-beta1 signalling induced a rapid relocation of Smad2 to the nucleus; in contrast, Smad4 remained localized to the cytoplasm unless it was coexpressed with Smad2."
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"Over-expressing activin receptor like kinase (ALK) 5, the TGF-beta type I receptor (TbetaRI) enhanced the up-regulation of Smad2, Smad3, MMP-9, and MMP-2 induced by TGF-beta1, whereas application of TbetaRI inhibitor SB431542 diminished the stimulatory effects of TGF-beta1 on these genes."
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"At a low concentration of 0.1 ng/ml TGF-beta1 activates Smad2 and Smad3 as well as their target genes, e.g. CTGF but not Id1."
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"Also, TGF-beta1 activated SMAD2 and SMAD1/5, an effect that was abolished by ALK5 inhibition."
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"Together, these results highlight that TGF-beta1 activates the Smad2 containing complex, which in turn interacts with Sp1 and enhances its binding to the GDP-fucose transporter promoter."
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"Acting via the canonical pathway, TGF-β1 activates (i.e. phosphorylates) Smad2 transcription factor and induces nuclear translocation of activated Smad2 xref ."
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"Others, however, have suggested that another T2 cytokine, IL-4, actually attenuates TGF-β1–stimulated connective tissue growth factor expression by inhibiting TGF-β1–induced ERK-1/2 and Smad-2 and Sma[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"CPB INHBA cells had a stronger pSmad2 signal than control cells when treated with TGFbeta1."
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"The membrane receptor, serine/threonine kinase complex, can be activated by TGF-beta1 and phosphorylate the transcription factors Smad1, Smad2 or Smad3 and then bind to Smad4, and travel to the nucleus XREF_BIBR - XREF_BIBR."
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"Here we confirmed Smad2 was activated (phosphorylated) by TGF-beta1 in a time dependent manner and the up-regulation of P-Smad2 was reduced in rosiglitazone treated ADPKD cyst lining epithelial cells."
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"Cannabinoid receptor type 2 agonist JWH133 reduced serum profibrotic cytokines levels of TGF-beta1 and inhibited TGF-beta1 and Smad2 pathway in vitro and in vivo."
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"Previous studies have found that TGF-β1 can activate both SMAD2 and SMAD3 [ xref ]."
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"Thapsigargin induced Ca2+ increase inhibits TGFbeta1 mediated Smad2 transcriptional responses via Ca2 +/calmodulin-dependent protein kinase II."
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"We then tested whether the biofilm treatment interfered with TGF-β1-induced Smad2 activation in GECs."
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"For instance, it was recently shown that SMAD2 and SMAD3 activation by TGFbeta1 could be inhibited by the Ras/MEK/Erk signaling pathway [40]."
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"The present results showed that TGF-beta1 had little effect on Smad3 and xCT expressions in SNU387 , SNU449 , SNU475 , and SK-Hep1 cells even though TGF-beta1 increased Smad2 / 3 phosphorylation levels ."
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"Smad2 phosphorylation is detected in HFSCs just prior to the transition from telogen to anagen, and Smad2 is activated by TGF-beta2, but not TGF-beta1 or TGF-beta3 produced by DP cells."
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"In the Smad-dependent pathway, TGF-b1 directly phosphorylates and activates the downstream mediator Smad2 and Smad3 through TGF-b receptor I, and then Smad2 and Smad3 bind Smad4, which forms a complex that moves into the nucleus and initiates gene transcription."
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"Both western blot and densitometry analysis confirm our finding that Ptn inhibited BMP4-mediated phosphorylation of BMP responsive SMAD1/5 in a dose-dependent manner (half maximal inhibitory concentration (IC 50 ) = 1.14 μM), ( xref ), but failed to attenuate SMAD2 activation by TGFβ1 at concentrations equal to or greater than those that were inhibitory to BMP signaling ( xref )."
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"In addition to fundamental differences in the mechanism of Smad2 and Smad3 activation by TGF-β1, at least in PDAC cells, our study reveals that Rac1 may drive tumourigenesis in carcinoma cells with a still intact TGF-β/Smad pathway by favouring resistance to TGF-β1-mediated growth inhibition and by increasing TGF-β1-induced cell migration at the R-Smad epigenetic level."
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"Both Smad-2 and p38 mitogen activated protein (MAP) kinase were rapidly activated by TGF-beta1, as demonstrated by the early induction of phosphorylated Smad-2 and p38 MAP kinase, respectively."
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"We show here that early events consisted of a trend toward increased expression of extracellular signal-regulated kinase (ERK), and then TGF-beta1 significantly induced the activation of p38 and Smad2 in a time-dependent manner."
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"In suppressing malignant behavior of breast cancer cells, curcumin down-regulates expression of TGF-beta1 to inactivate Smad2 and MMP-9."
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"These effects were associated with the inhibition of TGF-induced Smad2 activation, whereas the overexpression of Smad6 had no effect on the TGF-beta-induced changes in HKCs."
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"Smad2, as a signaling molecule, can be initially activated by TGFbeta1."
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"TGF-beta1 also induced activation of Smad2, JNK1/2, ERK1/2, and p38 within 5 to 15 minutes, with peak activation at 15 to 60 minutes."
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"The expression level of the phosphorylated Smad2 (pSmad2) slightly increased when the cells were treated with 20 ng/ml TGF-beta1."
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"Pioglitazone inhibited AP-1 reporter activity but not Smad binding elements reporter activity without affecting TGF-beta 1-induced activation of mitogen-activated protein kinases (MAPKs) or Smad2."
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"The silencing of HIF-1alpha and Smad3, but not Smad2 and HIF-2alpha rescued the downregulation of FENDRR by hypoxia and TGFbeta1."
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"Other advantages of our study included using side-by-side experiments that allowed direct comparison of Smad2 and Smad3 associated proteins in human epithelial cells that were treated with TGF-beta1 prior to purifying Smad containing complexes."
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"Moreover, our results strongly suggest that heat treatment inhibits TGF-β1-induced Smad2 activation in PANC-1 cells."
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"Accordingly, TGF-β1 induced Smad2 expression, and activation were suppressed by Bcl11b overexpression ( xref )."
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"Consistently, SMAD2 was activated by TGFbeta1 and inhibited by GLT or upon combination with cisplatin (XREF_FIG)."
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"Although TGF-beta1 also activates Smad2, our results suggest that this signalling protein is not implicated in the TGF-beta1-induced uPA expression."
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"Due to the low efficiency of Smad reporter gene transfection in ZO SMCs, we showed in HEK293T cells, that Smad2 mediated gene transcription is increased by TGF-beta1 and inhibited by SB203580."
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"Immunoblotting analysis revealed that IMM-H007 activated AMPK, decreased the expression of TGF-beta1, and inhibited the activation of Smad2 in heart tissues."
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"Specifically, normal nuclear accumulation of Smad2 and Smad4 heterocomplexes induced by TGF-beta1 is involved in carcinogenesis."
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"As the primary cytokine regulating hepatic satellite cell (HSC) function, TGF-beta1 activates, promotes, and stimulates HSC proliferation and differentiation by phosphorylating downstream signaling molecules Sma- and Mad related proteins 2 and 3 (Smad2 and Smad3)."
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"As shown in Figure XREF_FIG, treatment with iPSC-CM significantly inhibited the up-regulation of p-Smad2 and p-Smad3 proteins induced by TGF-beta1 in AECII."
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"TGF-beta1 induced the receptor complex activation causes Smad2 and Smad3 activation through direct C-terminal phosphorylation."
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"However, this extremely sensitive and potent effect of dasatinib, particularly in Panc-1 cells, may have resulted from combined inhibition of ALK5 and SRC since we have previously shown that SRC contributed to TGF-beta1-mediated cell migration without affecting TGF-beta1 and ALK5-induced activation of Smad2 and Smad3."
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"It demonstrated that the phosphorylation of Smad2 increased after treatment with TGF-beta1 for 10 min, the Smad2 phosphorylation reached the peak levels after treated with TGF-beta1 for 30 min."
29312546
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"In an NEC animal model, oral administration of the isoform TGF-beta1 activated the downstream effector Smad2 in intestine and significantly reduced NEC incidence."
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"The TGFbeta1 mediated increase in nuclear Smad2 was significantly reduced by more than 50% by DMOG, and was almost completely blocked upon incubation under hypoxic conditions."
27155083
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"Notably, JWH133 decreased the serum levels of TGF-beta1 and repressed TGF-beta1 and Smad2 signaling in vitro and in vivo."
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"Smad2 and Smad3 are activated through carboxy-terminal phosphorylation by TGFbeta1."
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"TGF-beta1 activated Smad2 and MAPK pathways in ADPKD cyst lining epithelial cells."
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"These results suggest that Ras-activated JMJD3 enhances TGF-β1-induced Smad2 and Smad3 activation through induction of syntenin expression."
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"Although TGF-beta1 primarily activates Smad2 and -3, in primary endothelial cells it also activates Smad1 and -5 through a heterodimeric receptor complex consisting of ALK5 and ALK1 [XREF_BIBR]."
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"Smad4 is a candidate tumor suppressor gene whose protein product acts as a cofactor that binds TGF-beta 1 receptor activated Smad2 and Smad3 and generates transcriptional complexes [17]."
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"TGF-beta1-induced activation of SMAD2, but not SMAD1/5, was abolished by ALK5 inhibition, an effect that associated with prevention of TGF-beta1-induced apoptosis."
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"In contrast, TGF-beta1 stimulation of most HCC cell lines resulted in upregulation of p-Smad2 and/or p-Smad3 (XREF_FIG; XREF_SUPPLEMENTARY)."
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"Upon activation by TGF-beta1, Smad2 and Smad3 are activated by C-terminal receptor mediated phosphorylation and oligomerized with Smad4 to form a complex, which preferentially relocates into the nucleus."
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"These results suggest that TNC and TGF-β1 activate SMAD2 and induce type I collagen expression through different mechanisms."
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"Furthermore, E64d suppressed TGF-β1-induced Smad2 and Smad3 activation and expression of fibronectin extra domain A (ED-A), an alternatively spliced fibronectin variant, and subsequently prevented cardiac fibroblast trans-differentiation into myofibroblast, which contributed to post-MI collagen and fibronectin synthesis and deposition."
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"Moreover, elevated TGF-β concentrations have been observed in sera of HCC patients ( xref ) and previous findings indicate that TGF-β1 constitutively activates Smad2 in an autocrine fashion ( xref )."
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"XREF_BIBR Western blots showed that Si-YAP1 knockdown significantly decreased expression levels of WAVE2, alpha-SMA and p-SMAD2 (XREF_FIG), in line with Pefani et al XREF_BIBR who reported that TGF-beta1 targets the Hippo pathway to facilitate YAP1 and SMAD2 signaling."
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"TGF-beta1-induced activation of SMAD2, but not SMAD1/5, was abolished by ALK5 inhibition, an effect that associated with prevention of TGF-beta1-induced apoptosis."
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"Rosiglitazone suppressed TGF-β1 induced Smad2 activation, while ERK1/2 and P38MAPK signals remained unaffected."
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"In the present study, it was observed that TGF-beta1 induced upregulation of p-SMAD2 and 3 expression, and that these changes were significantly inhibited by pretreatment with SYY."
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"It is possible that TGF-beta1 functions to activate SMAD2 and phospho-SMAD 2 and participates in the rescue of the palatal fusion."
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"Lastly, we investigated the effects of MSC-conditioned medium (MSC-CM) on TGF-β1-induced Smad2 activation and the EMT response of HPMCs."
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"To determine if WISP-1 was exerting a direct effect upon TGF-beta1 signaling we examined the phosphorylation of Smad-2 in cells treated with TGF-beta1 for 30 min and 8 hrs by western blot analysis."
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"Using the ROS osteoblast like cells, we demonstrated that TGF-beta1 activates Smad2 and Smad3 at the conserved TGF-beta receptor phosphorylation motif (SSXS) and the nuclear accumulation of activated Smad2 and Smad3 occurs in a time dependent fashion."
20432467
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"TGF-beta1 promotes EMT in ISK cells by activating the SMAD2 signalling pathway."
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"TGFbeta1 induced Smad2 signaling is one of the well known mechanisms that mediates airway remodeling in asthmatics XREF_BIBR."
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"To confirm this hypothesis, the expression of pSmad2 and Twist in HepG2 cells treated with TGFbeta1 was first detected."
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"Thus, we proposed a positive feedback loop for regulation of the process of HSCs activation ( xref ): Infection with schistosome parasites elicits the up-regulation of TGF-β1 and IL-13 expression, which in turn increases the expression of miR-21 in HSCs through activation of SMAD 2 and 3 proteins by TGF-β1 and SMAD1/5, 2 and 3 by IL-13."
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"However, TGF-beta1 and 3 can also activate the ALK5 and SMAD2 and 3 pathway (the canonical most studied pathway), leading to an anti-angiogenic effect XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"In ZO SMCs, the increase in Nox4 was attributed to the activation of Smad2 by TGF-β1."
20724704
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"TGF-beta1 typically induce Smad2 / 3 signaling , promoting matrix maintenance by inhibiting chondrocyte hypertrophy [ 29,30 ] and inducing the expression of matrix proteins like aggrecan and collagen II [ 24 ] , similar to Erk1 / 2 [ 24,32 ] ."
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"However, TGF-beta1 markedly increased p-Smad2, in the presence or absence of LPS (XREF_FIG), with a> 4 fold increase of p-Smad2 and total Smad2 by 30 minutes (XREF_FIG)."
21437904
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"WWP2 mediates the TGFbeta1 induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2."
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"As seen in the stable transfectants, dn Rac1 but not FRNK, a kinase-deficient mutant and endogenous inhibitor of p125 FAK [ xref ], abolished phosphorylation of Smad2 [data not shown] and thus attest to the Rac1-dependency of TGF-β1-induced Smad2 activation in PANC-1 cells."
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"Furthermore, TGF-beta1 increases steady-state levels of Smad2 mRNA in the TGF-beta1-sensitive pancreatic cancer cell line COLO-357."
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"In an in vitro model of pulmonary fibrosis, miR-486-5p mimic was shown to inhibit TGF-β1 activation of SMAD2 and further, decreased the protein levels of fibronectin, α-SMA and CTGF in mouse fibroblasts (NIH/3T3) [ xref ]."
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"Emodin also inhibited TGF-β1-induced Smad2, Smad3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediated the emodin-induced effects on TGF-β1-induced EMT."
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"TGF-beta1 can induce biological effects through transforming growth factor beta type I receptor (TGFbetaRI) and TGFbetaRII receptor, and activate Smad2 or Smad3."
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"The present study shows for the first time that the TGFbeta-R1 gene is expressed in the POA of prepubertal female rats, and that the TGFbeta1 peptide up-regulated both gene and protein expression of the receptor, as well as that of Smad 2 and Smad 3, downstream markers demonstrating receptor activation and confirming the involvement of this signaling pathway."
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"Analysis of expression of phosphorylated and total Smad2 and Smad3 in A549 cells untreated or treated with TGF-beta1 alone or in combination with alpha-PD-L1 or M7824 demonstrated the ability of M7824 to markedly prevent activation of both Smad2 and Smad3 in response to TGF-beta1."
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"TGF-beta1 stimulates the p 15Ink4B expression by inducing a complex assembly of Smad2, Smad3, Smad4, and Sp1 on its promoter."
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"After SK-N-SH cells were transfected with Smad2 and Smad3 plasmid and treated with TGF-beta1 for 72 h, western blot analysis showed that the protein expression levels of Smad2 and Smad3 were significantly higher in the transfection group (t = 19.11, P = 0.0027; t = 20.41, P = 0.0024) (XREF_FIG)."
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"Treatment of TGF-beta1 for 5 or 15 minutes increased p-Smad2 in WT MEFs indicating that TGF-beta1 stimulation in this particular experiment was really working (XREF_SUPPLEMENTARY)."
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"Western blot showed that activin A, TGFβ1 and TGFβ2 activated SMAD2, and that knockdown of Inha expression in TM3 cells enhanced both activin A- and TGFβ-induced SMAD2 activation."
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"TGFbeta1 leads to Smad2- and Smad3 dependent expression of negative regulators of receptor mediated endocytosis, hence preventing reabsorption of important proteins like albumin (Gekle et al., 2003)."
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"TGF-β1-activated SMAD2 and SMAD3 bind to the common mediator SMAD4."
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"The increases in fibronectin and collagen secretion were inhibited in CFs exposed to both TGF- beta 1 and tranilast.We have previously demonstrated that TGF- beta 1 induced pSmad2 with a peak inductio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"As far as Rac1 is concerned, we have shown earlier that Rac1 promotes TGF-β1 signalling in PDAC-derived cell lines towards a pro-metastatic outcome by enhancing TGF-β1-induced Smad2 activation, epithelial-mesenchymal transition (EMT), and random cell migration and invasion xref ."
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"As for BMPs, BMP pathway specific Smads are essential to induce astrocyte differentiation, because TGF-beta1, which activates TGF-beta pathway specific Smads, Smad2 and Smad3, is incapable of inducing[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11165238
sparser
"A time course study showed that RSPO1 and TGFβ1 activated Smad2 with similar dynamics ( xref )."
28939678
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"TGF- beta 1 induced pSmad2 in PTCs and CFs within 30 min, which was inhibited by tranilast."
16528248
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"To further elucidate the mechanism by which PXS64 exerts anti-fibrotic and anti-inflammatory effects, we examined the effect of PXS64 on TGFbeta1 induced Smad2, AKT and ERK1/2 activities in cultured human proximal tubular cells."
25658916
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"To confirm whether H3K4me3 formation at Snail TSS and recruitment of RbBP5 are consequence of SMAD2/3 binding, we performed ChIP assays in SMAD2 knockdown DU145 cells treated with or without TGF-Beta1, interference efficiency was measured by qRT-PCR and western blotting (XREF_SUPPLEMENTARY)."
27566588
sparser
"CXCL16 and LIF expression was dependent on TGF-β1 activation of Smad2 and Smad3."
23891907
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"Our results showed that TGF-beta1 up-regulated p-Smad2, p-Smad3, Beclin 1 and LC3beta-II/I conversion in Star treated NIH3T3 fibroblast, but TGF-betaR1 and ALK5 inhibitor LY-2157299 suppressed the upregulation effects of TGF-beta1."
26716641
sparser
"TGF-β1 activated the transcription factors, Smad2 and Smad3, by phosphorylation in a time-dependent manner and elevated collagen I protein, one of the well-known extracellular matrix (ECM) proteins, in a dose-dependent manner (data not shown)."
27790277
sparser
"TGFB1-induced activation of Smad 2, -3, -4 leads to direct inhibition of STAT5 transactivation and STAT5-mediated transcription of downstream target genes, including miR-590 [ xref ]."
28423658
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"Nicotinamide adenine dinucleotide phosphate oxidase (Nox) inhibitors, diphenyleneiodonium (DPI) and apocynin blocked TGF-beta1 mediated Smad2 linker region phosphorylation."
30417274
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"Here we confirmed that SB431542, a validated tool to evaluate cellular mechanisms mediated by endogenous TGF-beta1 XREF_BIBR, selectively induced an inhibition of p-SMAD2 signaling, which was rescued by TGF-beta1 treatment, suggesting a similar trend between p-SMAD2 and p-CREB levels."
26059637
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"TGF-beta1 and BMP-4 were used to induce pSmad2 and pSmad1/5/8, respectively, while endogenous levels of pERK1/2 and p-p38 MAPK were probed."
24380766
sparser
"Here we confirmed Smad2 was activated (phosphorylated) by TGF-β1 in a time-dependent manner and the up-regulation of P-Smad2 was reduced in rosiglitazone-treated ADPKD cyst lining epithelial cells."
22174924
eidos
"Upon activation by TGF-beta1 , Smad2 and Smad3 are activated by C-terminal receptor-mediated phosphorylation and oligomerized with Smad4 to form a complex , which preferentially relocates into the nucleus ( 42 ) ."
33732314
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"TGF-beta1 treatment significantly increased levels of collagen I, fibronectin, alpha-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells."
30584275
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"CTGF, CTGF mRNA, p-Smad2 and p-ERK1/2 of HLF-02 cells could be significantly up-regulated after treated with TGF-beta1, and these increases could be inhibited significantly by matrine."
20067105
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"Conversely, inhibition of Let-7g enhanced TGF-beta1 induced pSmad2, further suggesting that Let-7g is a key player in the modulation of TGF-beta1 signalling in ECs."
26862319
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"In this report, by using the IN Cell Analyzer 1000, the fluorescence cell imaging instrument, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) could regulate TGFbeta1 induced Smad2 activation in a PI3 kinase dependent manner."
16949833
eidos
"c WB analysis showed that TGF-beta1 increased the expression of Smad2 , and EMT markers ( vimentin , N-cadherin , MMP9 ) ."
| PMC
sparser
"In addition, our data also confirmed that TGF-β1 induced Smad-2 phosphorylation was not influenced by p38 MAPK inhibition, which confirms that TGF-β1-induced Smad-2 activation was not involved in AngII-induced reduction of PPARγ."
22095985
sparser
"Additionally, as shown in C, reporter assay analysis with SBE-Luc, which includes Smad binding elements (SBE), verified that the transcriptional activation of Smad2 and Smad3 by TGF-β1 appeared to be [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23419524
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"Probably, TGF-beta1 leads to Smad2- and Smad3 dependent expression of negative regulators of receptor mediated endocytosis."
14561830
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"However in human pulmonary artery endothelial cells, BMP9 can also stimulate Smad2 activation XREF_BIBR, and can enhance TGFbeta1 induced Smad2 and Smad3 phosphorylation XREF_BIBR."
31897223
sparser
"The result will be a seemingly endless cycle where TGF-β1-activated p-SMAD2 activates TRPV1 and in return TRPV1 activates SMAD2."
24098582
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"TGF-beta1 increases p-Smad2 in the presence of LPS."
21437904
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"To identify specific molecules that activate the SMAD proteins, we stimulated the mouse primary HSCs with recombinant TGF-beta1 and IL-13, respectively, and found that the TGF-beta1 activated the SMAD2 and 3 proteins while IL-13 activated all the SMAD proteins tested including SMAD1/5 (XREF_FIG)."
25546547
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"TGFbeta1 activation led to pSMAD2 mediated transcriptional elevation of downstream mediators, such as CTGF, and an auto-induction of TGFbeta1, respectively."
25348252
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"Our data showed that the p-Smad2 levels were indeed increased in HepG2 cells treated with TGF-beta1, which was also inhibited by SB431542 (XREF_FIG)."
28492136
sparser
"Activation of Smad2 and Smad3 by TGF-β1 is directly inhibited by SKI2162 in keratinocyte and fibroblast cells."
25686821
sparser
"Moreover, PAR2 depletion strongly decreased TGF-β1-induced Smad3 and Smad2 activation, and led to a failure of TGF-β1 to stimulate non-canonical e.g ."
27248167
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"The role of internalization in transforming growth factor beta1 induced Smad2 association with Smad anchor for receptor activation (SARA) and Smad2 dependent signaling in human mesangial cells."
15613484
sparser
"The phosphorylation of Erk1/2 MAPK induced by TGF-β1 was significantly reduced after pre-incubation with treprostinil as shown by Western blotting and image analysis in xref B. The TGF-β1-induced activation of Smad2 was only reduced in IPF-derived fibroblasts by treprostinil, but not in control fibroblasts ( xref C)."
| PMC
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"TGF-beta1 stimulated p-Smad2, p-TAK1, p-ERK, p-p38 and cyclooxygenase-2 (COX-2) protein expression."
33148869
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"Anti-TGF-beta antibody, at levels which completely blocked TGF-beta 1 induced smad2 translocation, strongly blocked EMD induced smad2 translocation."
12200968
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"Another member of the TGFbetasuperfamily, TGFbeta1, utilizes a similar receptor complex, TGFbetaRII (a type II receptor) and ALK5 (a type I receptor) and activates SMAD2, 3 signaling."
24714770
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"Because a number of cell specific interactions have been described between TGF-beta1-driven Smad signaling and the c-Jun N-terminal kinase (JNK) pathway, we have investigated the effects of JNK inhibition on TGF-beta1 activation of Smad2, inhibition of branching, induction of CTGF expression, and apoptosis in mouse embryonic lung explants."
19127219
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"TGFbeta1, which was used as a positive control for the induction of Smad2 phosphorylation, resulted in robust Smad2 activation across all tested cell lines."
26447543
sparser
"SMAD2 is also activated by the TGF p pathway; hence, both GDF 11 and SMAD2 are involved in islet cell proliferation and differentiation into beta cells."
28223232
sparser
"Although SMAD2 and SMAD3 are highly similar in their structure and although TGF-β1 activates both SMAD2 and SMAD3 in most cell types, it seems likely that these SMAD isoforms mediate different transcr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22814105
sparser
"To identify specific molecules that activate the SMAD proteins, we stimulated the mouse primary HSCs with recombinant TGF-β1 and IL-13, respectively, and found that the TGF-β1 activated the SMAD2 and 3 proteins while IL-13 activated all the SMAD proteins tested including SMAD1/5 ( xref )."
25546547
reach
"Although TGFbeta1 stimulus observably increased the SND1, T-Smad2, P-Smad2, Smad4 and MMP2 in SND1-HK cells (P < 0.05 ~ 0.001), these effects of TGFbeta1 were abrogated by SND1-knockdown in SND1-SH cells (P < 0.01 ~ 0.001; Figure XREF_FIG)."
28160566
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"TGF-beta1 induced shuttling of pSmad2 to the nucleus, occurring maximally at 30 min - 3 h. Treatment with CXCL9 also led to shuttling of pSmad2 from the cytoplasm to the nucleus, but to a much lesser extent and at later time points."
26268659
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"Signaling induced by TGFbeta1 drives formation of a complex consisting of DeltaNp63alpha, mutant p53, and SMAD2, which results in the repression of DeltaNp63alpha transcriptional activity while promoting SMAD2 activity, resulting in increased invasiveness and metastasis [XREF_BIBR]."
27924063
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"Similarly, when TTC3 expression was suppressed, the TGF-beta 1 -stimulated elevation of p-SMAD2, SMAD2, p-SMAD3, and SMAD3 were inhibited."
30696809
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"In ZO SMCs, the increase in Nox4 was attributed to the activation of Smad2 by TGF-beta1."
20724704
sparser
"Although TGF-β1 also activates Smad2, our results suggest that this signalling protein is not implicated in the TGF-β1-induced uPA expression ( Fig. 2 C)."
21798735
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"In the EMT of RTECs, smad2 and smad3 were mainly mediated by TGF-beta 1 XREF_BIBR."
21850266
sparser
"Specifically, TGF-β1 activates SMAD2, which triggers mTORC2 activation, resulting in AKT phosphorylation and stimulation of the motility of bladder cancer cells [ xref ]."
31842336
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"TGF-beta1 activates Akt, ERK and Smad2 pathways in chondrocytes."
18471442
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"For analysis of Smad2 and Smad3 activation by TGF-beta1, these authors used a single concentration of 100 nM dasatinib rather than providing a dose response curve with higher concentrations."
26588899
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"To determine whether this downregulation of IDH1 is dependent on canonical TGF-beta signalling, fibroblasts depleted of Smad2, Smad3 or Smad4 were treated with or without TGF-beta1."
29137396
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"Taken together, the results of present study demonstrated that TGF-beta1 activated both the smad2 and Erk and Akt cascades via its receptor on gingival epithelial cells, even though these two pathways have opposite roles in cell death and survival, and the culmination of these signaling events induced mitochondria dependent apoptosis in gingival epithelial cells."
25882870
eidos
"A major issue that was raised by these studies and remained unresolved is whether smad2 / 3 is activated by TGF-beta1 or TGF-beta2 ."
30297828
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"Rosiglitazone suppressed TGF-beta1 induced Smad2 activation, while ERK1/2 and P38MAPK signals remained unaffected."
22174924
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"TGFbeta1 signals through complexes of heterotrimeric transmembrane type I and type II receptors, activating Smad2 or 3 to form complexes with Smad4 and trigger transcriptional changes that drive EMT a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17980714
sparser
"TGFbeta1 induced activation of both Smad2 and extracellular signal-regulated kinases (ERK1/2)."
16301820
reach
"Western blot analysis revealed that both activin-A and TGF-beta1 activate Smad2 in zebrafish follicles."
18838125
sparser
"We have previously shown that TGF-β1-induced activation of both Smad2 and p38 MAPK is Rac1-dependent in PDAC-derived cells xref , xref ."
29229918
sparser
"Importantly, the activation of both Smad2 and Smad3 (p<0.05) by TGFβ1 was blocked by ALC."
24588206
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"The protein expression levels of Smad2 or Smad3 were not significant differed between cells treated with TGF-beta1."
28432277
sparser
"Dorsomorphin also blocked the BMP-dependent phosphorylation of R-Smad1/5/8 in cultured cells with an IC50 of 470 nM but not TGF-β1-induced activation of Smad2."
21505654
reach
"Based on the identification of downstream events of TGF-beta signaling transduction over the past several years, TGF-beta1 has been shown to activate Smad2 and Smad3, which are negatively regulated by Smad7, an inhibitor of TGF-beta signaling, through the ubiquitin-proteasome degradation mechanism [XREF_BIBR]."
28171717
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"As expected, TGF-beta1 activates Smad1 and Smad2 in these cells."
20955695
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"Notably, Smad3 and Smad2 are differentially activated by TGFbeta1 in HSCs; in quiescent HSCs, TGFbeta1 receptor activation promotes Smad2 phosphorylation, whereas in transdifferentiated HSCs, it promotes Smad3 phosphorylation."
20890948
sparser
"Whereas others have shown that ERK inhibition decreased TGF-β1–induced Smad-2 and Smad-3 activation in human airway smooth muscle cells and TIMP-1 expression in a murine system, we report that inhibit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17418380
sparser
"As expected, TGF-β1 activates Smad1 and Smad2 in these cells."
20955695
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"Consequently, TGF-beta1 mediates the activation of p-Smad2, which further stimulates the cardiac specific transcription factors, and ultimately contributes to the facilitative effect of CNTs on BASC cardiogenesis."
27660434
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"TGF-beta1 induces Smad2 activation."
19506550
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"TGF-beta1 may activate both ALK5 and smad2 and MEK and ERK signaling pathways."
26001858
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"We show here that early events consisted of a trend toward increased expression of extracellular signal regulated kinase (ERK), and then TGF-beta1 significantly induced the activation of p38 and Smad2 in a time dependent manner."
19574221
sparser
"RAC1 and its ability to produce ROS has been shown to be required for efficient TGFβ1-induced activation of SMAD2 and p38 MAPK in keratinocytes and PDAC cells [ xref , xref , xref ] and in the latter type of cells both events are required for adherence-dependent TGFβ induction of BGN [ xref ]."
33266416
reach
"Here, we demonstrate that thapsigargin mediated increase of intracellular Ca (2+) concentrations inhibited TGFbeta1 induced Smad2 transcriptional activity in the oligodendroglial cell line OLI-neu."
20717921
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"The present study is consistent with this view, as we have demonstrated that tranilast inhibits TGF- beta 1 induced CTGF mRNA expression and TGF- beta 1 induced pSmad2."
16528248
sparser
"TGF-β1 activates type I receptor-phosphorylated (p-) Smad2, which interacts with Smad3 and Smad4 and then translocate to the nucleus for active transcription of fibrotic related genes, such as Collagen Type I α 1 Chain (COL1A1), Collagen Type III α 1 Chain (COL3A1), connective tissue growth factor (CTGF) and fibronectin ( xref , xref )."
33760134
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"ChIP assay using Smad2 antibody demonstrated that TGF-beta1 could increase the interaction of Smad2 with the ILK promoter and thereby ILK expression."
27177845
sparser
"Whereas blocking of ERK1/2 or p38 failed to inhibit TGF-beta1-induced Smad2 activation, inhibition of Smad2 by Smad7 overexpression inhibited the phosphorylation of ERK1/2 but not p38 in response to TGF-beta1."
15716330
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"In addition, the phosphorylation levels of smad2 induced by stimulation with TGFbeta1 were also decreased when the expression of LRG was suppressed, suggesting that LRG enhanced TGFbeta1 mediated smad2 signaling in Hep3B cells."
25826092
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"Western blot analysis also showed that the protein expression of the transcription factor Gli2 did not significantly differ after SK-N-SH cells were transfected with Smad2 and Smad3 plasmid or SiRNA Smad2/3 and treated with TGF-beta1 for 72 h (F = 1.643, P = 0.3297; t = 2.614, P = 0.0602) (XREF_FIG), indicating that the increase in Gli2 expression after treatment with TGF-beta1 was not related to Smad2 or Smad3 overexpression or knockdown."
28393230
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"Smad2, Smad3, and Smad4 are present and activated by TGF-beta1 in human mesangial cells."
10504488
sparser
"Activation of Smad2 by MEK1 or TGF beta 1 resulted in an enhanced nuclear localization of Smad2, which was inhibited upon blocking MEK1 activity."
11448947
reach
"CXCL16 and LIF expression was dependent on TGF-beta1 activation of Smad2 and Smad3."
23891907
sparser
"For instance, it was recently shown that SMAD2 and SMAD3 activation by TGFβ1 could be inhibited by the Ras/MEK/Erk signaling pathway ."
15023526
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"But the activation of Smad2, ERK1/2 and p38MAPK pathways induced by TGF-beta1 were not blocked by rosiglitazone, which suggested other pathways except Smad2 and MAPK pathways might be involved in the anti-fibrosis effect of rosiglitazone."
22174924
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"UDCA-LPE also decreased phosphorylated Smad3 and Smad2 directly induced by TGF-beta1."
25041068
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"To verify our assumption, TGF-beta1-stimulated NRK52E cells were co-cultured with two concentrations of CTS (10 and 20 muM) for 1 h. TGF-beta1 treatment dramatically increased p-Smad2 and p-Smad3 but did not influence Smad4."
29928474
eidos
"Interestingly , TGFbeta1 was able to significantly activate Smad2 / 3 signaling with the introduction of an Alk5-like beta4beta5 loop ."
35005539
sparser
"Using cultured rat renal NRK-49F fibroblasts, we report that LXA₄ (1 nM) inhibits TGF-β1 (10 ng/ml)-induced activation of Smad2 and MAP-kinases (P<0.05), and furthermore, LXA₄ reduced TGF-β1-stimulated PAI-1 luciferase activation (P<0.05) relative to vehicle-stimulated cells."
21628447
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"Although TGF-beta1 could activate Smad2, ERK1/2 and p38MAPK pathways, rosiglitazone had no effect on TGF-beta1-induced activation of these three pathways (XREF_FIG)."
22174924
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"Importantly, JWH133 reduced serum profibrotic cytokines levels of TGF-beta1 and inhibited TGF-beta1 and Smad2 pathway in vitro and in vivo."
29262578
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"TGF-beta1 signals through the heteromeric complex of TGF-beta type I and type II receptors to activate Smad2 and Smad3."
24973329
sparser
"We went on to show that Rac1 modulates TGF-β1-signalling in PDAC cells by suppressing and promoting, respectively, TGF-β1-induced activation of Smad3 and Smad2, eventually resulting in protection of PDAC cells from excessive growth inhibition by TGF-β1 and in enhanced cell migration (chemokinesis)."
21624123
sparser
"The treatment with ALK5 inhibitor (SB505124) provoked a dramatic inhibition of TGF-β1-induced Smad2 and Smad3 activation ( Fig. 1 C)."
21798735
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"In our experiments, TGF-beta1 activated the SMAD2 pathway in all studied SCs, including EndoSC, indicating their sensitivity at the reception and signaling levels."
33718358
sparser
"TGF-β1 is a well-known profibrotic cytokine that plays key pathological roles, including EMT promotion, in peritoneal fibrosis in patients undergoing the PD. xref TGF-β1 activates Smad2 and Smad3, which consequently induces a molecular transition that results in the downregulation of the intracellular adhesion molecule E-cadherin and upregulation of mesenchymal-associated molecules, such as Snail, α-SMA, and fibronectin."
28624215
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"20 During TGF-beta pathway mediated hypertrophic scar formation, there is an up-regulation of SMAD-2 and SMAD-3, as well as increased expression of TGF-beta1, TbetaRI and TbetaRII, which lead to positive feedback loop."
28303029
sparser
"Although TGF-β1 primarily activates Smad2 and -3, in primary endothelial cells it also activates Smad1 and -5 through a heterodimeric receptor complex consisting of ALK5 and ALK1 [ xref ]."
22522454
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"To determine the optimal dose for TGF-beta1-induced Smad2 phosphorylation, cardiac fibroblasts were treated with increasing concentrations of TGF-beta1 for 30 min."
21897055