IndraLab
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"TGF-beta1 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 alpha 1 Chain (COL1A1), Collagen Type III alpha 1 Chain (COL3A1), connective tissue growth factor (CTGF) and fibronectin."
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"Importantly, inhibition of the clathrin-independent, lipid raft pathway, but not of the clathrin-dependent pathway, results in decreased TGF-beta1 induced Smad2 and p38 phosphorylation, supporting a specific role for clathrin-independent endocytosis of T beta RIII in regulating both Smad-dependent and Smad-independent TGF-beta signaling."
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"In SKOV3 cells, TGF-beta1 alone induced phosphorylation of SMAD2 and SMAD3, denoting the activation of these two R-SMADs; co-treatment with OFE reduced the levels of p-SMAD2 (4mug/mL, P = 0.002 vs. control group; 20mug/mL, P = 0.001 vs. control group) and p-SMAD3 (4mug/mL, P = 0.035 vs. control group; 20mug/mL, P = 0.004 vs. control group), whereas the total expression of SMAD2/3 remained unchanged."
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"Moreover, we also investigated the potential anti-fibrotic properties of ML290 by evaluating its ability to promote markers such as matrix metalloproteinase (MMP)-2 and inhibit the pro-fibrotic actions of TGF-β1-induced Smad-2 and Smad-3 phosphorylation in primary human cardiac fibroblasts, representing key fibrosis-producing cells."
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"The results showed that TGF-β1 markedly induced Smad2 phosphorylation and up-regulated the expression level of TGFBR2 and vimentin proteins but reduced E-cadherin expression ( xref , lanes 2 and 3 vs. lane 1), suggesting that TGFBR2/Smad2 signaling mediates TGF-β1-induced EMT in PCa cells."
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"Jang et al showed that inhibiting the TGF-β type I receptor, activin receptor-like kinase 5 (ALK5) using the synthetic inhibitor IN-1130 suppresses the subsequent TGF-β1-induced phosphorylation of Smad2 and Smad3 and nuclear accumulation of Smad proteins in human fibroblasts of PD-plaque."
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"Among its three isoforms, namely TGF-beta1, 2 and 3, all types of renal cells total can produced TGF-beta1 [XREF_BIBR] and acts as a pro fibrotic regulator in several ways : i) Fibrotic proteins such as FN and collagen I can be induced by TGF-beta1independently; and ii) TGF-beta1 can induced the phosphorylation of Smad2 and Smad3, and then formed the oligomeric complexes includingSmad2, Smad3 and Smad4 [XREF_BIBR]."
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"Among its three isoforms, namely TGF-β1, 2 and 3, all types of renal cells total can produced TGF-β1 [ xref ] and acts as a pro-fibrotic regulator in several ways: i) Fibrotic proteins such as FN and collagen I can be induced by TGF-β1independently; and ii) TGF-β1 can induced the phosphorylation of Smad2 and Smad3, and then formed the oligomeric complexes includingSmad2, Smad3 and Smad4 [ xref ]."
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"Instead, our findings show that galunisertib treatment of aNK cells in vitro inhibits TGFβ1-induced SMAD2 phosphorylation and significantly restores expression of DNAM-1, NKp30, NKG2D, and TRAIL and release of perforin and granzyme A, which could contribute to the observed reversal of TGFβ1-mediated inhibition of cytotoxicity."
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"Likewise, adenovirus mediated overexpression of Smad7, a natural inhibitor of Smad signaling, impaired both TGF-beta1- and FBG induced phosphorylation of Smad2 and prevented the FBG domain from inducing EMT in NMuMG cells, as observed by phase-contrast microscopy and the impaired decrease of E-cadherin gene expression."
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"Compared to the effect of SB431542, a known TGF-β Type I receptor inhibitor ( xref ), TGF-β1-induced Smad2 phosphorylation remained relatively unaffected by our compounds in this time frame, suggesting that the effect of heterotaxin on Smad2 phosphorylation in vivo may not involve direct inhibition of TGF-β receptors or may inhibit a non-smad-dependent TGF-β signaling pathway ( xref )."
"Down-regulation of glypican-1 expression by stable transfection of a full-length glypican-1 antisense construct resulted in decreased anchorage-dependent and -independent cell growth in Colo-357 pancreatic cancer cells and attenuated TGF-beta1 induced cell growth inhibition, Smad2 phosphorylation, and PAI-1 promoter activity"
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"To determine how TGF-β1 regulates collagen III and fibronectin expression, we treated HPMCs with 5 ng/ml of TGF-β1; subsequent western blot analysis showed that TGF-β1 induced phosphorylation of Smad 2 and 3 starting at 10 min post-treatment and reached a maximum between 30-60 min, but TGF-β1 did not affect the total Smad 2 and 3 expression levels (Figure xref )."
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"The results indicate that there was a remarkable promotion of TGF-β1-induced Smad2 phosphorylation in BASCs grown on CNT-Col matrices compared to the control group ( xref ), indicating that the facilitative effect of CNTs on cardiac differentiation of BASCs might be attributed to the activation of TGF-β1 signaling."
"The sentence (Jubilant) TGFB induces phosphorylation of SMAD2 is inhibited by SB-431542 , an inhibitor of ALK4, ALK5 and ALK7. is translated to Complex of ACVR1B (Homo sapiens) Protein and TGFB1 (Homo sapiens) Protein The following edits have been made already none Links Doc Sourcerer for 12065756 ACVR1B (Homo sapiens) Protein TGFB1 (Homo sapiens) Protein"
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"Additionally, Smad2 phosphorylation and N-cadherin up-regulation induced by TGF-beta1 or a combination of TGF-beta1 and TNF-alpha or TWEAK was completely inhibited by SB431542 (10muM), an inhibitor of the TGF-beta receptor type 1 (TbetaRI) kinase, which is known to be an activator of the Smad pathway."
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"In contrast to an Activin receptor-like kinase 5 (Alk5) inhibitor, C8 and GSK3008348 failed to inhibit TGF-β1 induced SMAD3 and SMAD2 phosphorylation, but inhibited TGF-β-induced phosphorylation of ERK1/2 and STAT3, suggesting that αVβ1 integrin is involved in non-canonical TGF-β signaling pathways."
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"Hepatic mRNA (XREF_FIG) and protein (XREF_FIG) levels of transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), collagen I (Col-1), Smad4, phosphorylated Smad2 (p-Smad2), and phosphorylated Smad3 (p-Smad3) were significantly increased in MCD diet fed mice, which were blunted by Hemin administration."
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"In the TGF-β signaling pathway, TGF-β1 receptor kinases phosphorylate Smad2 and Smad3 in the C-terminal residue, which further forms a complex with Smad4 and promotes nuclear translocation of the complex to regulate downstream gene expression, resulting in stimulation of EMT [ xref – xref ]."
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"In cultured HK-2 cells, TGF-beta1 dramatically up-regulated TbetaRI expression and phosphorylated levels of Smad 2 and Smad 3, but down-regulated Smad7 expression, consistent with the data in vivo, and confirmed the characteristics of TGF-beta and Smads signaling in EMT [XREF_BIBR]."
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"Down-regulation of glypican-1 expression by stable transfection of a full-length glypican-1 antisense construct resulted in decreased anchorage dependent and -independent cell growth in Colo-357 pancreatic cancer cells and attenuated TGF-beta1 induced cell growth inhibition, Smad2 phosphorylation, and PAI-1 promoter activity."
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"TGF-beta1 binds to TGF-beta type I receptor, a transmembrane protein with Ser/Thr kinase domain, and then phosphorylates Smad2 and Smad3, which regulates the expression of downstream target genes and subsequently contributes to promoting EMT and metastasis of many cancer cells [XREF_BIBR]."
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"[XREF_BIBR; XREF_BIBR] More recently, specific TGFbeta inhibitors, EW-705, EW-7195 and EW-7197, have been shown to disrupt EMT in TGFbeta treated breast cancer cells as well as in in vivo using the 4T1 orthotopic xenograft mouse model [XREF_BIBR; XREF_BIBR; XREF_BIBR] Compounds in clinical trials that may interfere with the EMT by blocking the TGFbeta pathway include LY2157299, a TGFbeta1 receptor inhibitor that specifically downregulates the phosphorylation of SMAD2."
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"In SKOV3 cells, TGF-β1 alone induced phosphorylation of SMAD2 and SMAD3, denoting the activation of these two R-SMADs; co-treatment with OFE reduced the levels of p-SMAD2 (4 μg/mL, P = 0.002 vs. control group; 20 μg/mL, P = 0.001 vs. control group) and p-SMAD3 (4 μg/mL, P = 0.035 vs. control group; 20 μg/mL, P = 0.004 vs. control group), whereas the total expression of SMAD2/3 remained unchanged (Fig. xref )."
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"In contrast to an Activin receptor like kinase 5 (Alk5) inhibitor, C8 and GSK3008348 failed to inhibit TGF-beta1 induced SMAD3 and SMAD2 phosphorylation, but inhibited TGF-beta-induced phosphorylation of ERK1/2 and STAT3, suggesting that alphaVbeta1 integrin is involved in non canonical TGF-beta signaling pathways."
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"The activated type I receptors then propagate the signal by phosphorylating a family of transcription factors, called receptor-activated Smads ( R-Smads ). xref , xref BMP receptors activate Smad1, Smad5 and Smad8, whereas Smad2 and Smad3 are phosphorylated by the activin and the TGF-[BETA]β receptors."
"The ability of TGF-beta1 to induce BGN mRNA was critically dependent on Smad signaling, since 1) the up-regulation of BGN mRNA was preceded by a marked increase in Smad2 phosphorylation in TGF-beta1-treated PANC-1 cells, 2) TGF-beta1 was unable to induce BGN mRNA in pancreatic carcinoma cell lines that carry homozygous deletions of the Smad4/DPC4 gene, 3) inhibition of the Smad pathway in PANC-1 cells by transfection with a dominant negative Smad4/DPC4 mutant significantly reduced TGF-beta1-induced BGN mRNA expression, 4) stable reintroduction of wild type Smad4/DPC4 into Smad4-null CFPAC-1 cells restored the TGF-beta1 effect,"
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"In our study, TGF-β1-stimulated Smad2 phosphorylation in HIFs was insensitive to a PI3 kinase inhibitor (Akt inhibitor; LY294002), suggesting that TGF-β1-stimulated Smad2 phosphorylation occurs independently of the PI3 kinase/Akt pathway, which is similar to previous reports [ xref , xref ]."
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"We show that: (i) GT1-1 cells express Smad 2, 3, 4, and 7; (ii) TGFbeta1 enhances the phosphorylation of Smad 2 and 3 at short times of exposure (15-30 min); (iii) TGFbeta1 induces the synthesis of the inhibitory Smad 7 at longer times (60-120-240 min); (iv) the conditioned medium of type 1 astrocytes enhances the phosphorylation of Smad 2 and 3 in GT1-1 cells and a TGFbeta1 neutralising antibody counteracts this effect."
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"Activation of Smad proteins is known to be the key signaling pathway of the profibrotic effect of TGF-beta1, AM at 10(-8) M exerted no effect on TGF-beta1-induced Smad2 phosphorylation, but prevented the suppression of the inhibitory Smad6 protein by TGF-beta1 and restored Smad2-Samd6 complex formation."
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"Phosphorylation of Smad2 and differentiation of smooth muscle cells can be rescued by exogenous TGF-beta1 in the yolk sac culture, consistent with the idea that lower levels of TGF-beta or reduced responsiveness required for receptor activation play a role in HHT pathogenesis [XREF_BIBR]."
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"However, co-treatment with TSA completely prevented TGF-beta1-induced morphologic changes and significantly prevented TGF-beta1-induced downregulation of E-cadherin and upregulation of collagen type I. Treatment with TSA did not alter TGF-beta1-induced phosphorylation of Smad2 and Smad3 but induced several inhibitory factors of TGF-beta1 signals, such as inhibitors of DNA binding/differentiation 2 (Id2) and BMP-7."
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"We show that : (i) GT1-1 cells express Smad 2, 3, 4, and 7; (ii) TGFbeta1 enhances the phosphorylation of Smad 2 and 3 at short times of exposure (15-30 min); (iii) TGFbeta1 induces the synthesis of the inhibitory Smad 7 at longer times (60-120-240 min); (iv) the conditioned medium of type 1 astrocytes enhances the phosphorylation of Smad 2 and 3 in GT1-1 cells and a TGFbeta1 neutralising antibody counteracts this effect."
"TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, was also suppressed by VEGF. VEGF attenuation of TGF-beta action was also demonstrated in two other endothelial cell lines. In conclusion, VEGF attenuates TGF-beta action in the human endothelial cell, specifically at the level of transcription of PAI-1 gene and Smad2/3 phosphorylation"
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"Whereas BMP-2 induced Smad1/5 phosphorylation and TGF-β1 induced Smad2 phosphorylation, expression of TβRIII only modestly inhibited BMP-2–induced Smad1/5 phosphorylation (Supplemental Figure S3A), and had no effect on TGF-β1–induced Smad2 phosphorylation (Supplemental Figure S3B)."
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"Most importantly, they found that ATRA alone or in combination with UDCA repressed CYP7A1 expression in human hepatocytes, and significantly inhibited collagen 1A1 (COL-1A1), matrix metalloproteinase-2 (MMP-2), and α-smooth muscle actin (α-SMA) expression and/or activity in primary human hepatic stellate cells (HSCs) and LX-2 cells (a HSC cell line), and TGF-β1 induced Smad2 phosphorylation in LX-2 cells."