IndraLab
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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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"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."
sparser
"The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC)."
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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."
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"Given that SKIP depletion decreased Smad3 activation [XREF_BIBR], and that we have previously reported Smad3 as essential for TGF-beta1-induced uPA in transformed cells [XREF_BIBR], we can speculate that the reduction of Smad3 activation by TGF-beta1 may inverse the cell response to the growth factor, while in basal conditions the effect of SKIP on uPA expression may be independent of Smad3 signalling."
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"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]."
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"The importance of these genes that are highly expressed in hORMDL3 zp3-Cre mice to airway remodeling and asthma is suggested from studies demonstrating expression of these pathways in the airways of human asthmatics, induction of these mediators by allergen inhalation in asthmatics (TGF-beta1, MMP-9), and inhibition of asthma outcomes in mice deficient in these genes (ADAM-8, Smad3, MMP-9), or in mice treated with neutralizing antibodies (TGF-beta1)."
sparser
"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."
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)."
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"To further examine whether PDGF-C is involved in the inhibitory role of PAA on the Smad3 and MAPK signaling activation induced by TGF-beta1, the expression of proteins associated with the Smad3 and MAPK pathways were measured by western blotting in cells treated with or without TGF-beta1, PAA and PDGF-C."
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"These findings suggested that in the combined TNFalpha+ TGFbeta1 stimulation each cytokine activated its respective canonical pathway -- TNFalpha activated p65 and TGFbeta1 activated Smad3 -- and that the functional cooperativity between TNFalpha+ TGFbeta1 was due to cooperative activities of p65 and Smad3."
sparser
"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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"To examine this hypothesis, three types of small molecule inhibitors were used : (1) Ly294002, a PI3K inhibitor was used as a control to ensure that the enhanced response was not due to cell proliferation, (2) PF573228 was used to block integrin mediated FAK activation, and (3) SIS3 was utilized to inhibit TGF-beta1 mediated SMAD3 signaling."
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."
sparser
"To further examine whether PDGF-C is involved in the inhibitory role of PAA on the Smad3 and MAPK signaling activation induced by TGF-β1, the expression of proteins associated with the Smad3 and MAPK pathways were measured by western blotting in cells treated with or without TGF-β1, PAA and PDGF-C. The results showed that the increased expression of proteins associated with the Smad3 and MAPK pathway induced by TGF-β1 was significantly reduced after PAA treatment ( xref )."
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"For example, the targeting of both TGFbeta1 and SMAD3 transcripts might possibly allow resveratrol to impair TGFbeta1 induced SMAD3 dependent promotion of cell motility and invasiveness in advanced stages of gastric cancer [XREF_BIBR, XREF_BIBR] or when SMAD2 and SMAD3 phosphorylated at both linker and COOH-terminal regions transmit malignant TGFbeta1 signal in later stages of human CRC [XREF_BIBR]."
eidos
"TGF-beta signaling plays a crucial role in fibrosis.41 ,42 It was persistently activated in many types of fibrosis.41 ,43 It has been reported that TGF-beta1 can activate Smad3 , and the latter induce transcription of pro-fibrotic agents , factors that can interference this signaling pathway may cause fibrosis ."
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"Microarray analysis of Smad3 wildtype and null keratinocytes treated with TGFbeta1 for 48 hours showed that most cell cycle associated genes analyzed in the earlier data set (XREF_FIG) were downregulated by TGFbeta1 in both Smad3 wildtype, Smad3 null and Smad3 wildtype and v-ras Ha keratinocytes but this downregulation was abolished in Smad3 null and v-ras Ha keratinocytes (XREF_FIG), and XREF_SUPPLEMENTARY."
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"As shown in XREF_FIG, FXR activation markedly downregulated the TGFbeta1 induced Smad3 (but had no influence on the expression of FXR, Smad2 and Smad4) in HKC cells (XREF_FIG), which was significantly alleviated by the FXR antagonist guggulsterone (GS) (XREF_FIG) and the ectopic expression of Smad3 (XREF_FIG)."
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"In conclusion, our results showed that TGF-beta1 can induce the stabilization of HIF-1alpha in PDLSCs under nonhypoxic conditions, that HIF-1alpha can negatively regulate the TGF-beta1 and Smad3 signal pathway in PDLSCs, and that TGF-beta1 and HIF-1alpha can synergistically inhibit the osteogenesis of PDLSCs."
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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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"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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"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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"Generating a panel of PC3 prostate cancer cells expressing alphavbeta6 or alphavbeta6 and beta3cyto or alphavbeta3 and beta6cyto chimeras, these authors reported that alphavbeta6 co-precipitated with TGFBRII, a relationship that required the cytoplasmic tail of beta6 and that physical association was required for the TGFbeta1 dependent upregulation of SMAD3, which in turn upregulated MMP2."
sparser
"Previous studies have confirmed that the inhibition of JNK1 activation prevents the TGF-β1-induced Smad3 activation and nuclear translocation (Liu et al., 2012), and the upregulation of the TGF-β1 receptor on hepatic stellate cells is in a JNK-dependent manner (Thomas et al., 2015)."
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"We have recently demonstrated that disruption of canonical TGF-beta1 signaling in Smad3 -/- mice reduced flexor tendon adhesions and improved tendon gliding, due to reduced extracellular matrix (ECM) deposition, but led to compromised biomechanical properties with a significant reduction in repair strength 4."
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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."
eidos
"It is now well established that Smad3 is a common downstream signaling molecule and transcriptional factor leading to tissue fibrosis.9 Indeed , Smad3 can be activated not only by TGF-beta1 but also by many pathogenic mediators , including Ang II , advanced glycation end products ( AGEs ) , and C-reactive protein ( CRP ) via the p38 / ERK MAPK-Smad crosstalk pathway.6 , 7 , 8,24,25 It is also known that Smad3 binds many collagen promoters to trigger fibrogenesis.10 Thus , mice lacking Smad3 are protected against fibrosis in many diseases , including hypertensive renal and cardiovascular diseases.11 , 12 , 13 , 14 , 15 These findings strongly suggest that targeting Smad3 may represent promising research into the new drug development for treating diseases with progressive fibrosis ."
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"A large number of M1 macrophages with proinflammatory characteristics are rapidly recruited to cardiac tissues, and M1 macrophages stimulate myocardial fibrosis by inducing the production of TGF-beta1, while TGF-beta1 stimulates Smad3 signaling, induces the production of collagen and MMP, and releases extracellular matrix from cardiac fibroblasts to promote tissue fibrosis and myocardial remodeling 144."