Gene Symbol: Smad2
Description: SMAD family member 2
Alias: Madh2, mothers against decapentaplegic homolog 2, SMAD 2, mad-related protein 2, mothers against DPP homolog 2
Species: rat
Products:     Smad2

Top Publications

  1. Wang D, Kanuma T, Mizunuma H, Takama F, Ibuki Y, Wake N, et al. Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer. Cancer Res. 2000;60:4507-12 pubmed
    ..including transforming growth factor beta (TGF-beta) receptor type I (RI), TGF-beta receptor type II (RII), Smad2, Smad3, and Smad4/DPC4, have been identified in the transduction pathway of the tumor suppressor TGF-beta...
  2. Maliekal T, Antony M, Nair A, Paulmurugan R, Karunagaran D. Loss of expression, and mutations of Smad 2 and Smad 4 in human cervical cancer. Oncogene. 2003;22:4889-97 pubmed available on Smad alterations in cervical cancer and so we probed, for the first time, for alterations in Smad 2 and Smad 4 genes using human cervical cancer cell lines and human cervical tissue samples...
  3. Sekimoto G, Matsuzaki K, Yoshida K, Mori S, Murata M, Seki T, et al. Reversible Smad-dependent signaling between tumor suppression and oncogenesis. Cancer Res. 2007;67:5090-6 pubmed
    ..TGF-beta activates both its type I receptor (TbetaRI) and c-Jun NH2-terminal kinase (JNK), which phosphorylate Smad2 and Smad3 at the COOH-terminal (pSmad2/3C) and linker regions (pSmad2/3L)...
  4. Li H, Han M, Bernier M, Zheng B, Sun S, Su M, et al. Krüppel-like factor 4 promotes differentiation by transforming growth factor-beta receptor-mediated Smad and p38 MAPK signaling in vascular smooth muscle cells. J Biol Chem. 2010;285:17846-56 pubmed publisher
    ..KLF4 was found to transduce TGF-beta1 signals via phosphorylation-mediated activation of Smad2, Smad3, and p38 MAPK...
  5. Macias Silva M, Abdollah S, Hoodless P, Pirone R, Attisano L, Wrana J. MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell. 1996;87:1215-24 pubmed
    ..Thus, transient association and phosphorylation of MADR2 by the TGFbeta receptor is necessary for nuclear accumulation and initiation of signaling. ..
  6. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113:685-700 pubmed
    ..This article reviews these latest advances and presents our current understanding on the mechanisms of TGF-beta signaling from cell membrane to the nucleus. ..
  7. Lin X, Duan X, Liang Y, Su Y, Wrighton K, Long J, et al. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 2006;125:915-28 pubmed
    ..PPM1A dephosphorylates and promotes nuclear export of TGFbeta-activated Smad2/3...
  8. Zhou S, Zawel L, Lengauer C, Kinzler K, Vogelstein B. Characterization of human FAST-1, a TGF beta and activin signal transducer. Mol Cell. 1998;2:121-7 pubmed
    ..different in sequence from its Xenopus counterpart, hFAST-1 shared with xFAST-1 the ability to bind to human Smad2 and activate an activin response element (ARE)...
  9. Vrljicak P, Myburgh D, Ryan A, Van Rooijen M, Mummery C, Gupta I. Smad expression during kidney development. Am J Physiol Renal Physiol. 2004;286:F625-33 pubmed
    ..Based on the observed patterns of expression, we speculate that individual or combinations of Smads may play specific roles in cell-fate determination during kidney development. ..

More Information


  1. Park S, Cho H, Jeong Y, Shin J, Kang J, Park K, et al. Melittin inhibits TGF-β-induced pro-fibrotic gene expression through the suppression of the TGFβRII-Smad, ERK1/2 and JNK-mediated signaling pathway. Am J Chin Med. 2014;42:1139-52 pubmed publisher
    ..Melittin dramatically inhibited the phosphorylation of TGFβRII and Smad2/3...
  2. Chi C, Liu X, Hou F, Yu X, Li C, Cui L, et al. Herbal compound 861 prevents hepatic fibrosis by inhibiting the TGF-?1/Smad/SnoN pathway in bile duct-ligated rats. BMC Complement Altern Med. 2018;18:52 pubmed publisher
    ..Protein and mRNA changes for SnoN and TGF-?1/Smad signaling (TGF-?1, Smad2, phosphorylated Smad2 [p-Smad2], phosphorylated Smad3 [p-Smad3], fibronectin, and collagen III) were determined by ..
  3. Brennan J, Lu C, Norris D, Rodriguez T, Beddington R, Robertson E. Nodal signalling in the epiblast patterns the early mouse embryo. Nature. 2001;411:965-9 pubmed
    ..Both of these functions are independent of Smad2. Moreover, Nodal signals from the epiblast also pattern the visceral endoderm by activating the Smad2-dependent ..
  4. Jin M, Lee J, Lee K, Jin Z, Pak J, Kim H. Alteration of TGF-β-ALK-Smad signaling in hyperoxia-induced bronchopulmonary dysplasia model of newborn rats. Exp Lung Res. 2016;42:354-364 pubmed
    ..each time point were evaluated for the expression of TGF-β1, ALK1, ALK5, phosphorylated Smad1/5, phosphorylated Smad2/3, VEGF, and endoglin, as accessed by both biochemical and immunohistological analyses...
  5. Zhan C, Tang J, Zhou D, Li Z. Effects of tanshinone IIA on the transforming growth factor β1/Smad signaling pathway in rat cardiac fibroblasts. Indian J Pharmacol. 2014;46:633-8 pubmed publisher
    ..At the end of the culture treatment, the mRNA expression of FN and the expression of phosphorylated Smad2/3 (p-Smad2/3) increased significantly (P < 0.01)...
  6. Zhang Y, Zhang Q, Guo X, Zhang H, Liu L. IGFBPrP1 induces liver fibrosis by inducing hepatic stellate cell activation and hepatocyte apoptosis via Smad2/3 signaling. World J Gastroenterol. 2014;20:6523-33 pubmed publisher
    ..The expression of Smad2/3 and p-Smad2/3 was examined by Western blot and immunohistochemistry...
  7. Bugyei Twum A, Advani A, Advani S, Zhang Y, Thai K, Kelly D, et al. High glucose induces Smad activation via the transcriptional coregulator p300 and contributes to cardiac fibrosis and hypertrophy. Cardiovasc Diabetol. 2014;13:89 pubmed publisher
    ..the activity of the transcriptional co-activator p300, leading to the activation of TGF-? via acetylation of Smad2; and that by inhibiting p300, TGF-? activity will be reduced and heart failure prevented in a clinically relevant ..
  8. Zhang S, Fei T, Zhang L, Zhang R, Chen F, Ning Y, et al. Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation. Mol Cell Biol. 2007;27:4488-99 pubmed
    ..Furthermore, Smad7 repressed Smad3/4-, Smad2/4-, and Smad1/4-enhanced reporter gene expression, indicating that Smad7 can function independently of type I ..
  9. Hao J, Wang B, Jones S, Jassal D, Dixon I. Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro. Am J Physiol Heart Circ Physiol. 2000;279:H3020-30 pubmed
    ..Losartan administration (8 wk, 15 mg. kg(-1). day(-1)) normalized total Smad 2 overexpression in infarct scar and remnant heart tissue and normalized Smad 4 in infarct scar...
  10. Nakagawa T, Li J, Garcia G, Mu W, Piek E, Bottinger E, et al. TGF-beta induces proangiogenic and antiangiogenic factors via parallel but distinct Smad pathways. Kidney Int. 2004;66:605-13 pubmed
    ..of VEGF-A and TSP-1 by TGF-beta1 in NRK52E cells was associated with activation of pathway-restricted R-Smads (Smad2 and 3) and blocking these Smads by overexpression of Smad7 blocked their induction...
  11. Hua Y, Li S, Lai J, Liang L, Peng B, Liang H, et al. [Changes in TGF-beta1/Smads signaling pathway in rats with chemical hepatocarcinogenesis]. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28:1848-52 pubmed
    ..The protein expressions of TGF-beta1, phosphorylated Smad2, Smad4 and Smad7 were detected in these rats with immunohistochemistry, and the mRNA expression of Smad4 was ..
  12. He J, Chen S, Huang Y, CHEN Y, Dong Y, Ma H. The nonpeptide AVE0991 attenuates myocardial hypertrophy as induced by angiotensin II through downregulation of transforming growth factor-beta1/Smad2 expression. Heart Vessels. 2010;25:438-43 pubmed publisher
    ..myocardial hypertrophy and whether these AVE0991 effects involved transforming growth factor beta1 (TGF-beta1) and Smad2. A rat model of neonatal myocardial hypertrophy was induced by AngII...
  13. Hata A, Lagna G, Massague J, Hemmati Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 1998;12:186-97 pubmed
    ..Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy. ..
  14. Kadry M, Ali H. Downregulation of HIF1-?, Smad-2, AKT, and Bax gene expression in sodium nitrite-induced lung injury via some antioxidants. J Biochem Mol Toxicol. 2017;31: pubmed publisher
    ..Interestingly the combination regimen showed the most significant effect. ..
  15. Chong P, Ozdamar B, Wrana J, Forman Kay J. Disorder in a target for the smad2 mad homology 2 domain and its implications for binding and specificity. J Biol Chem. 2004;279:40707-14 pubmed
    The Smad2 Mad homology 2 (MH2) domain binds to a diverse group of proteins which do not share a common sequence motif...
  16. Wu R, Zhang Y, Feng X, Derynck R. Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4. Mol Cell Biol. 1997;17:2521-8 pubmed
    ..These results correlate the ability of individual Smads to homomerize with transcriptional activation and additionally with their biological activity in mammalian cells. ..
  17. Zhao J, Ding W, Song N, Dong X, Di B, Peng F, et al. Urotensin II-induced collagen synthesis in cultured smooth muscle cells from rat aortic media and a possible involvement of transforming growth factor-?1/Smad2/3 signaling pathway. Regul Pept. 2013;182:53-8 pubmed publisher
    ..The mRNA and protein expressions of TGF-?1, collagen I, Smad2 and Smad3 were determined using Real-time RT-PCR and Western blotting...
  18. Kretschmer A, Moepert K, Dames S, Sternberger M, Kaufmann J, Klippel A. Differential regulation of TGF-beta signaling through Smad2, Smad3 and Smad4. Oncogene. 2003;22:6748-63 pubmed
    ..b>Smad2, Smad3 and Smad4 expression were selectively inhibited in differentiation-competent cells by using improved ..
  19. Zhang Y, Kanzaki M, Furukawa M, Shibata H, Ozeki M, Kojima I. Involvement of Smad proteins in the differentiation of pancreatic AR42J cells induced by activin A. Diabetologia. 1999;42:719-27 pubmed
    ..The expression of Smad proteins was determined by northern blotting. Phosphorylation and translocation of Smad2 was measured by transfecting flag-tagged Smad2...
  20. Al Rasheed N, Fadda L, Attia H, Ali H, Al Rasheed N. Quercetin inhibits sodium nitrite-induced inflammation and apoptosis in different rats organs by suppressing Bax, HIF1-?, TGF-?, Smad-2, and AKT pathways. J Biochem Mol Toxicol. 2017;31: pubmed publisher
    ..Quercetin administration is recommended in areas of high altitudes to combat the hazard effect of hypoxia in different organs and in some diseases accompanied by hypoxic stress. ..
  21. Liu Y, Liu R, Liu W, Liu L, Wu Z, Chen Y. [Effects of Chinese herbal medicine Yiqi Huoxue Formula on TGF-?/smad signal transduction pathway and connective tissue growth factor in rats with renal interstitial fibrosis]. Zhong Xi Yi Jie He Xue Bao. 2010;8:1165-73 pubmed
    ..Kidneys of the rats were taken out, and mRNA and protein expressions of TGF-?, smad2, smad7 and CTGF were measured with real-time fluorescent quantitative reverse transcription-polymerase chain ..
  22. Vincent S, Dunn N, Hayashi S, Norris D, Robertson E. Cell fate decisions within the mouse organizer are governed by graded Nodal signals. Genes Dev. 2003;17:1646-62 pubmed
    ..Here we removed Smad2 activity in the epiblast, using a conditional inactivation strategy...
  23. Nakajima T, Yanagihara M, Nishii H. Temporal and regional patterns of Smad activation in the rat hippocampus following global ischemia. J Neurol Sci. 2014;337:25-37 pubmed publisher
    ..detected in the rat hippocampus by means of western blot and immunohistochemistry; 2) after 5 min of ischemia, Smad2 and Smad3 proteins accumulated in the nuclei of pyramidal cells in the CA1 region, which is vulnerable to ischemia;..
  24. Chen T, Nie H, Gao X, Yang J, Pu J, Chen Z, et al. Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway. Toxicol Lett. 2014;226:150-62 pubmed publisher understand the mechanism, we used human pulmonary epithelial cell line A549 to investigate the role of TGF-?/p-Smad2 signaling pathway in EMT...
  25. Vonica A, Brivanlou A. The left-right axis is regulated by the interplay of Coco, Xnr1 and derrière in Xenopus embryos. Dev Biol. 2007;303:281-94 pubmed
    ..We conclude that derrière, Xnr1, and Coco define a posttranscriptionally regulated signaling center, which is a necessary link in the signaling chain leading to an increased TGF-beta signal on the left side of the embryo. ..
  26. Li R, Liang L, Dou Y, Huang Z, Mo H, Wang Y, et al. Mechanical stretch inhibits mesenchymal stem cell adipogenic differentiation through TGFβ1/Smad2 signaling. J Biomech. 2015;48:3665-71 pubmed publisher
    ..Alternatively, stretch upregulated phosphorylation of Smad2. This stretch-induced increase in Smad2 phosphorylation was suppressed by pretreatment with the TGFβ1/Smad2 ..
  27. Li P, Oparil S, Novak L, Cao X, Shi W, Lucas J, et al. ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells. J Appl Physiol (1985). 2007;102:390-8 pubmed
    ..osteopontin, and plasminogen activator inhibitor-1 mRNA and protein, but not TGF-beta1-induced phosphorylation of Smad2 and Smad3...
  28. Waldrip W, Bikoff E, Hoodless P, Wrana J, Robertson E. Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell. 1998;92:797-808 pubmed
    Smad proteins transmit TGFbeta signals from the cell surface to the nucleus. Here we analyze Smad2 mutant embryos created using ES cell technology...
  29. Ito Y, Zhao J, Mogharei A, Shuler C, Weinstein M, Deng C, et al. Antagonistic effects of Smad2 versus Smad7 are sensitive to their expression level during tooth development. J Biol Chem. 2001;276:44163-72 pubmed
    ..Here we tested the hypothesis that antagonistic effects between Smad2 and Smad7 regulate TGF-beta signaling during tooth development...
  30. Nawshad A, Hay E. TGFbeta3 signaling activates transcription of the LEF1 gene to induce epithelial mesenchymal transformation during mouse palate development. J Cell Biol. 2003;163:1291-301 pubmed
    ..When phospho-Smad2 and Smad4 are present in the nucleus, LEF1 is activated without beta-catenin...
  31. Zhao Y, Geverd D. Regulation of Smad3 expression in bleomycin-induced pulmonary fibrosis: a negative feedback loop of TGF-beta signaling. Biochem Biophys Res Commun. 2002;294:319-23 pubmed
    ..TGF-beta signals are mediated by a family of Smad proteins, of which Smad2 and Smad3 are downstream intracellular targets of serine/threonine kinase receptors of TGF-beta...
  32. Xu F, Zhou D, Meng X, Wang X, Liu C, Huang C, et al. Smad2 increases the apoptosis of activated human hepatic stellate cells induced by TRAIL. Int Immunopharmacol. 2016;32:76-86 pubmed publisher
    ..We have previously shown that Smad2 protects against hepatic fibrogenesis; however, the role of Smad2 in the regulation of activated HSC apoptosis ..
  33. Peng F, Xiao Z, Chen H, Chen Y, Zhou J, Yu H, et al. Parathyroid hormone inhibits TGF-?/Smad signaling and extracellular matrix proteins upregulation in rat mesangial cells. Biochem Biophys Res Commun. 2016;478:1093-8 pubmed publisher
    ..The results showed that PTH pretreatment prevented TGF-?1 and high glucose-induced Smad2/3 phosphorylation and consequent upregulation of fibronectin and type IV collagen within 4 h...
  34. Liu Y, Meyer C, Muller A, Herweck F, Li Q, Mullenbach R, et al. IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF-?-independent Smad signaling. J Immunol. 2011;187:2814-23 pubmed publisher
    ..Smad1 and Smad2 were identified as the key mediators of IL-13-dependent CTGF expression...
  35. Wang E, Ma E, Woodruff T. Activin signal transduction in the fetal rat adrenal gland and in human H295R cells. J Endocrinol. 2003;178:137-48 pubmed
    ..This suggests that in the adrenal gland the components of the activin receptor/Smad pathway are dynamically changing in the transition from fetal to neonatal life, and are important to the function of this organ. ..
  36. Chou Y, Wang H, Chen Y, Danielpour D, Yang Y. Cited2 modulates TGF-beta-mediated upregulation of MMP9. Oncogene. 2006;25:5547-60 pubmed
    ..This is the first demonstration that Cited2 functions as a Smad3/p300-interacting transcriptional co-activator in modulating the expression of MMP9, which could affect tumor cell invasion mediated by TGF-beta. ..
  37. Cardillo M, Lazzereschi D, Gandini O, Di Silverio F, Colletta G. Transforming growth factor-beta pathway in human renal cell carcinoma and surrounding normal-appearing renal parenchyma. Anal Quant Cytol Histol. 2001;23:109-17 pubmed
    ..Our data support the concept that the reduction of T beta RII and SMAD proteins in renal cell carcinomas is involved in tumor development and suggest an altered TGF-beta/SMAD signaling pathway in kidney neoplasia. ..
  38. Mori S, Matsuzaki K, Yoshida K, Furukawa F, Tahashi Y, Yamagata H, et al. TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions. Oncogene. 2004;23:7416-29 pubmed
    ..In conclusion, HGF and TGF-beta transmit the signals through JNK-mediated R-Smads phosphorylation at linker regions. ..
  39. Wilkinson D, Ogden S, Stratton S, Piechan J, Nguyen T, Smulian G, et al. A direct intersection between p53 and transforming growth factor beta pathways targets chromatin modification and transcription repression of the alpha-fetoprotein gene. Mol Cell Biol. 2005;25:1200-12 pubmed
    ..of AFP-expressing hepatoma cells with transforming growth factor-beta1 (TGF-beta1) induced SnoN transcription and Smad2 activation, concomitant with AFP repression...
  40. Ring C, Ogata S, Meek L, Song J, Ohta T, Miyazono K, et al. The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-containing transcription factor in activin/nodal signaling. Genes Dev. 2002;16:820-35 pubmed
    ..Williams-Beuren syndrome critical region 11 (XWBSCR11), and further, show that it interacts with pathway-specific Smad2 and Smad3 in a ligand-dependent manner...
  41. Subramanian S, Polikandriotis J, Kelm R, David J, Orosz C, Strauch A. Induction of vascular smooth muscle alpha-actin gene transcription in transforming growth factor beta1-activated myofibroblasts mediated by dynamic interplay between the Pur repressor proteins and Sp1/Smad coactivators. Mol Biol Cell. 2004;15:4532-43 pubmed
    ..Physical association of Pur proteins with Smad2/3 was observed as was binding of Smads to an upstream enhancer region that undergoes DNA duplex unwinding in ..
  42. Massague J. TGFbeta in Cancer. Cell. 2008;134:215-30 pubmed publisher
    ..The mechanistic basis and clinical relevance of TGFbeta's role in cancer is becoming increasingly clear, paving the way for a better understanding of the complexity and therapeutic potential of this pathway. ..
  43. Zhang Y, Feng X, Derynck R. Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature. 1998;394:909-13 pubmed
    ..This mechanism of transcriptional activation by TGF-beta, through functional and physical interactions between Smad3-Smad4 and c-Jun-c-Fos, shows that Smad signalling and MAPK/JNK signalling converge at AP1-binding promoter sites. ..
  44. Bristol Gould S, Hutten C, Sturgis C, Kilen S, Mayo K, Woodruff T. The development of a mouse model of ovarian endosalpingiosis. Endocrinology. 2005;146:5228-36 pubmed
    ..endosalpingiosis has been developed by directing a dominant-negative version of the TGF-beta transcription factor, Smad2, to the ovary using the Müllerian-inhibiting substance promoter (MIS-Smad2-dn)...
  45. Beaudoin M, Snook L, Arkell A, Stefanson A, Wan Z, Simpson J, et al. Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats. Obesity (Silver Spring). 2014;22:1632-42 pubmed publisher
    ..ZDF ROSI exhibited decreased phosphorylation of SMAD2 and SMAD3 exclusively in scWAT, along with increases in inhibitory SMAD7 and the E3 ubiquitin ligase SMURF2...
  46. Wu L, Qiu W, Sun J, Wang J. SENP1 attenuates the liver fibrosis through down-regulating the expression of SMAD2. Biochem Biophys Res Commun. 2018;495:755-760 pubmed publisher
    ..collagen I, collagen III, ?-SMA and TGF-?1 were inspected using quantitative real-time PCR (qRT-PCR), as well as SMAD2. Subsequently, the relative mRNA and protein level of SENP1 was also determined via qRT-PCR and western blot ..
  47. Yao R, Lemon W, Wang Y, Grubbs C, Lubet R, You M. Altered gene expression profile in mouse bladder cancers induced by hydroxybutyl(butyl)nitrosamine. Neoplasia. 2004;6:569-77 pubmed
    ..Using the pathway visualization tool GenMAPP, we found that several genes, including TbR-I, STAT1, Smad1, Smad2, Jun, NFkappaB, and so on, in the TGF-beta signaling pathway and p115 RhoGEF, RhoGDI3, MEKK4A/MEKK4B, PI3KA, and ..
  48. Palaniyandi S, Ferreira J, Brum P, Mochly Rosen D. PKC?II inhibition attenuates myocardial infarction induced heart failure and is associated with a reduction of fibrosis and pro-inflammatory responses. J Cell Mol Med. 2011;15:1769-77 pubmed publisher
    ..Further, a 90% decrease in active TGF?1 and a significant reduction in SMAD2/3 phosphorylation indicated that the selective inhibition of PKC?II attenuates cardiac remodelling mediated by the ..
  49. Wang H, Liu S, Liu S, Wei W, Zhou X, Lin F, et al. Enhanced expression and phosphorylation of Sirt7 activates smad2 and ERK signaling and promotes the cardiac fibrosis differentiation upon angiotensin-II stimulation. PLoS ONE. 2017;12:e0178530 pubmed publisher
    ..Sirt7 depletion could largely reverse Ang-II induced increase of nuclear translocalization and activity of smad2 and extracellular regulated kinases (ERK) in CFs...
  50. Hu X, Rui W, Wu C, He S, Jiang J, Zhang X, et al. Compound Astragalus and Salvia miltiorrhiza extracts suppress hepatocarcinogenesis by modulating transforming growth factor-?/Smad signaling. J Gastroenterol Hepatol. 2014;29:1284-91 pubmed publisher
    ..The results suggest that CASE significantly suppresses HCC progression by mediating TGF-?/Smad signaling, especially by modulating Smad3 phosphorylation both at the C-terminal and linker region. ..
  51. Fernandez D, Tuma D, Tuma P. Hepatic microtubule acetylation and stability induced by chronic alcohol exposure impair nuclear translocation of STAT3 and STAT5B, but not Smad2/3. Am J Physiol Gastrointest Liver Physiol. 2012;303:G1402-15 pubmed publisher
    ..cytoplasm by microtubule attachment until ligand activation, we examined transforming growth factor-β-induced Smad2/3 translocation. We found that ethanol exposure selectively impaired translocation of the STATs, but not Smad2/3...
  52. Baburajendran N, Jauch R, Tan C, Narasimhan K, Kolatkar P. Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers. Nucleic Acids Res. 2011;39:8213-22 pubmed publisher
    ..However, the R-Smads Smad1, Smad2 and Smad3 homodimerize with substantially decreased efficiency despite pronounced structural similarities to Smad4...
  53. Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, et al. TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J. 1997;16:5353-62 pubmed
    ..b>Smad2 and Smad3 are structurally highly similar and mediate TGF-beta signals...
  54. Ning W, Tao L, Liu C, Sun J, Xiao Y, Hu J, et al. [Effect of enalapril on the expression of TGF-beta1, p-Smad2/3 and Smad7 in renal interstitial fibrosis in rats]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009;34:27-34 pubmed
    ..fibrosis by observing the effect of enalapril on the expression of transforming growth factor-beta1(TGF-beta1), p-Smad2/3 and Smad7 in renal tissuess of unilateral urethral obstruction (UUO) rat model...
  55. Maeda S, Hayashi M, Komiya S, Imamura T, Miyazono K. Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J. 2004;23:552-63 pubmed
  56. Zakrzewicz A, Kouri F, Nejman B, Kwapiszewska G, Hecker M, Sandu R, et al. The transforming growth factor-beta/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension. Eur Respir J. 2007;29:1094-104 pubmed
    ..The current study examined whether perturbations to the TGF-beta/Smad2,3 signalling axis occurred in a monocrotaline (MCT) rodent model of experimental PAH...
  57. Drummond A, Dyson M, Le M, Ethier J, Findlay J. Ovarian follicle populations of the rat express TGF-beta signalling pathways. Mol Cell Endocrinol. 2003;202:53-7 pubmed
    ..It remains to be established however, as to which follicle subtypes these pathways are active in. ..
  58. Liu F, Pouponnot C, Massague J. Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes. Genes Dev. 1997;11:3157-67 pubmed
    ..Smad4 is not required for nuclear translocation of Smads 1 or 2, or for association of Smad2 with a DNA binding partner, the winged helix protein FAST-1...
  59. Yang J, Kan M, Wu G. Bergenin ameliorates diabetic nephropathy in rats via suppressing renal inflammation and TGF-β1-Smads pathway. Immunopharmacol Immunotoxicol. 2016;38:145-52 pubmed publisher showed that BEG markedly reduced transforming growth factor-β1 (TGF-β1) production, down-regulated p-Smad2/3 expression and promoted Smad7 expression both in vivo and in vitro...
  60. Organista Juárez D, Carretero Ortega J, Vicente Fermín O, Vázquez Victorio G, Sosa Garrocho M, Vazquez Prado J, et al. Calcium-sensing receptor inhibits TGF-?-signaling by decreasing Smad2 phosphorylation. IUBMB Life. 2013;65:1035-42 pubmed publisher
    ..Wild type CaSR interferes with TGF-?-dependent Smad2 phosphorylation and induces its proteasomal degradation, resulting in a decrease of TGF-?-dependent ..
  61. Zhang H, Akman H, Smith E, Zhao J, Murphy Ullrich J, Batuman O. Cellular response to hypoxia involves signaling via Smad proteins. Blood. 2003;101:2253-60 pubmed
    ..Exposure of HUVECs to hypoxia resulted in phosphorylation and nuclear transportation of Smad2 and Smad3 proteins as well as stimulation of transcriptional activities of Smad3 and the transcription factor ..
  62. Nakano A, Koinuma D, Miyazawa K, Uchida T, Saitoh M, Kawabata M, et al. Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins. J Biol Chem. 2009;284:6109-15 pubmed publisher
    ..Pin1 interacted with Smad2 and Smad3 but not Smad4; this interaction was enhanced by the phosphorylation of (S/T)P motifs in the Smad linker ..
  63. Ng Y, Chen Y, Tsai T, Lan X, Yang W, Lan H. Pentoxifylline inhibits transforming growth factor-beta signaling and renal fibrosis in experimental crescentic glomerulonephritis in rats. Am J Nephrol. 2009;29:43-53 pubmed publisher
    ..PTX may be an anti-fibrosis agent capable of inhibiting renal fibrosis in a rat model of crescentic glomerulonephritis. Blockade of TGF-beta1 expression and Smad2/3 activation may be a mechanism by which PTX inhibits renal fibrosis.
  64. Labbe E, Silvestri C, Hoodless P, Wrana J, Attisano L. Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2. Mol Cell. 1998;2:109-20 pubmed the gsc promoter, but efficient transcriptional activation and assembly of a DNA-binding complex of FAST2, Smad2, and Smad4 requires an adjacent Smad4 site...
  65. Goto Y, Nomura M, Tanaka K, Kondo A, Morinaga H, Okabe T, et al. Genetic interactions between activin type IIB receptor and Smad2 genes in asymmetrical patterning of the thoracic organs and the development of pancreas islets. Dev Dyn. 2007;236:2865-74 pubmed
    ..Here, we provide genetic evidence that ActRIIB and Smad2 genes cooperatively regulated asymmetrical patterning of the thoracic organs and pancreas development in mice...
  66. Wang N, Ren G, Zhou Z, Xu Y, Qin T, Yu R, et al. Cooperation of myocardin and Smad2 in inducing differentiation of mesenchymal stem cells into smooth muscle cells. IUBMB Life. 2012;64:331-9 pubmed publisher
    ..Of note, myocardin cooperated with Smad2 to synergistically activate SM22? promoter and significantly enhance the expression of SM22?...
  67. Liu Y, Wang L, Zou H, Song X, Xu H, Lin P, et al. Expression and location of Smad2, 4 mRNAs during and after liver fibrogenesis of rats. World J Gastroenterol. 2006;12:1577-82 pubmed
    To investigate the location alteration of Smad2 and Smad4 mRNAs in the liver during and after fibrogenesis in rats. Eighty male Wistar rats weighing approximately 200 g each were used...
  68. Zhang J, Pho V, Bonasera S, Holtzman J, Tang A, Hellmuth J, et al. Essential function of HIPK2 in TGFbeta-dependent survival of midbrain dopamine neurons. Nat Neurosci. 2007;10:77-86 pubmed
    ..These data underscore the importance of the TGFbeta-Smad-HIPK2 pathway in the survival of DA neurons and its potential as a therapeutic target for promoting DA neuron survival during neurodegeneration. ..
  69. Topper J, Cai J, Qiu Y, Anderson K, Xu Y, Deeds J, et al. Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc Natl Acad Sci U S A. 1997;94:9314-9 pubmed
  70. Li T, Si G, Chen F. [Effects of Shenqi Jiedu Decoction on expressions of transforming growth factor-beta1, smad2 and smad3 in renal tissues of rats with chronic renal failure induced by adenine]. Zhong Xi Yi Jie He Xue Bao. 2010;8:263-8 pubmed
    ..a compound traditional Chinese herbal medicine, on expressions of transforming growth factor beta1 (TGF-beta1), smad2 and smad3 proteins in renal tissues of rats with chronic renal failure (CRF) induced by adenine, and to explore ..
  71. Lee M, Tsai M, Sun P, Chien L, Cheng A, Ma N, et al. Phyto-power dietary supplement potently inhibits dimethylnitrosamine-induced liver fibrosis in rats. Food Funct. 2013;4:470-5 pubmed publisher
    ..These data indicate that the phyto-power dietary supplement may inhibit the TGF-?1/Smad signaling and relieve liver damage in experimental fibrosis. ..
  72. Upton P, Davies R, Trembath R, Morrell N. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells. J Biol Chem. 2009;284:15794-804 pubmed publisher
    ..Contrary to expectations, BMP9 also stimulated Smad2 activation. Furthermore, BMP9 induced the expression of interleukin 8 and E-selectin...
  73. Gong W, Yan M, Chen J, Chaugai S, Chen C, Wang D. Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosis through inhibition of transforming growth factor β-induced Smad signaling. Front Med. 2014;8:445-55 pubmed publisher
    ..but did not block TAC-induced transforming growth factor-β1 (TGF-β1) production and phosphorylation of Smad2/3...
  74. Li M, Li C, Liu Y, Xing Y, Hu L, Borok Z, et al. Mesodermal deletion of transforming growth factor-beta receptor II disrupts lung epithelial morphogenesis: cross-talk between TGF-beta and Sonic hedgehog pathways. J Biol Chem. 2008;283:36257-64 pubmed publisher
    ..To our knowledge, this is the first in vivo evidence for a reciprocal and novel mode of cross-communication between Shh and TGF-beta pathways during embryonic development. ..
  75. Liu Y, Festing M, Thompson J, Hester M, Rankin S, El Hodiri H, et al. Smad2 and Smad3 coordinately regulate craniofacial and endodermal development. Dev Biol. 2004;270:411-26 pubmed
    ..TGF-beta, activins, and nodal ligands operate through the highly homologous Smad2 and Smad3 intracellular mediators...
  76. Quinn Z, Yang C, Wrana J, McDermott J. Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins. Nucleic Acids Res. 2001;29:732-42 pubmed
    ..Our studies indicate that Smad2 and 4 (Smad2/4) complexes cooperate with MEF2 regulatory proteins in a GAL4-based one-hybrid reporter gene assay...
  77. Gao J, Zhao W, Xue F, Zhou L, Xu S, Ding N. Early administration of propofol protects against endotoxin-induced acute lung injury in rats by inhibiting the TGF-beta1-Smad2 dependent pathway. Inflamm Res. 2010;59:491-500 pubmed publisher
    ..injury and on the expression of transforming growth factor (TGF)-beta1 and the downstream target of TGF-beta1, Smad 2, in the lung tissues in the endotoxic rats...
  78. Davis B, Hilyard A, Lagna G, Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature. 2008;454:56-61 pubmed publisher
  79. Wang X, Zhu Y, Tao H, Jin C, Liu Y, Lu X, et al. Interaction of ERK1/2 and Smad2/3 signaling pathways in TGF-?1-induced TIMP-3 expression in rat chondrocytes. Arch Biochem Biophys. 2014;564:229-36 pubmed publisher
    ..In this study, our data suggest TGF-?1 induces TIMP-3 expression through activations of both the ERK1/2 and Smad2/3 signaling pathways...
  80. Wu S, Capasso L, Lessa A, Peng J, Kasisomayajula K, Rodriguez M, et al. High tidal volume ventilation activates Smad2 and upregulates expression of connective tissue growth factor in newborn rat lung. Pediatr Res. 2008;63:245-50 pubmed publisher
    ..Temporal expression of TGF-betas, p-Smad2, Smad7, and CTGF was analyzed...
  81. Li J, Li X, Xu W, Wang S, Hu Z, Zhang Q, et al. Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGF?/Smad signalling pathways. Liver Int. 2015;35:1222-33 pubmed publisher
    ..HSCs were found to undergo apoptosis and decreased expression of p-Smad2 and p-AKT in luteolin-treated animals...
  82. Shi Y, Gao J, Xu S, Zhao W. [Changes in pulmonary transforming growth factor-beta1/smad2 signaling pathway in a two-hit pulmonary injury as a result of uncontrolled hemorrhagic shock and lipopolysaccharide in rats]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008;20:401-4 pubmed
    To investigate the changes in pulmonary transforming growth factor-beta1 (TGF-beta1)/smad2 signaling pathway in pulmonary injury as a result of hemorrhagic shock followed by lipopolysaccharide challenge...
  83. Huang D, Wang Y, Wang L, Zhang F, Deng S, Wang R, et al. Poly(ADP-ribose) polymerase 1 is indispensable for transforming growth factor-? Induced Smad3 activation in vascular smooth muscle cell. PLoS ONE. 2011;6:e27123 pubmed publisher
    ..PARP1 is indispensable for TGF-?1 induced Smad3 activation in rat VSMCs. Targeting PARP1 may be a promising therapeutic approach against vascular diseases induced by dysregulation of TGF-?/Smad3 pathway. ..
  84. Dunn N, Vincent S, Oxburgh L, Robertson E, Bikoff E. Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo. Development. 2004;131:1717-28 pubmed
    TGFbeta/activin/Nodal receptors activate both Smad2 and Smad3 intracellular effector proteins. The functional activities of these closely related molecules have been extensively studied in cell lines...
  85. Izzi L, Silvestri C, Von Both I, Labbé E, Zakin L, Wrana J, et al. Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development. EMBO J. 2007;26:3132-43 pubmed
    ..As Gsc is itself induced in a Foxh1-dependent manner, we propose that Foxh1 initiates positive and negative transcriptional circuits to refine cell fate decisions during gastrulation. ..
  86. Zhao X, Zhao L, Zheng Q, Su J, Guan H, Shang F, et al. Chymase induces profibrotic response via transforming growth factor-beta 1/Smad activation in rat cardiac fibroblasts. Mol Cell Biochem. 2008;310:159-66 pubmed
    ..blot assay demonstrated that chymase not only increased TGF-beta1 expression but also upregulated phosphorylated-Smad2/3 protein...