Gene Symbol: Smad3
Description: SMAD family member 3
Alias: Madh3, Smad 3, mad3, mothers against decapentaplegic homolog 3, MAD (mothers against decapentaplegic, Drosophila) homolog 3, MAD homolog 3, mothers against DPP homolog 3
Species: rat
Products:     Smad3

Top Publications

  1. Chai J, Wu J, Yan N, Massague J, Pavletich N, Shi Y. Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding. J Biol Chem. 2003;278:20327-31 pubmed
    ..The crystal structure of a Smad3 MH1 domain bound to a palindromic DNA sequence, determined at 2...
  2. TSAI S, Hollenbeck S, Ryer E, Edlin R, Yamanouchi D, Kundi R, et al. TGF-beta through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation. Am J Physiol Heart Circ Physiol. 2009;297:H540-9 pubmed publisher
    ..was to better understand the role of transforming growth factor-beta (TGF-beta) and its primary signaling protein Smad3 in the development of intimal hyperplasia...
  3. Massague J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91 pubmed
    ..Mutations in these pathways are the cause of various forms of human cancer and developmental disorders. ..
  4. 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
    ..This work demonstrates that PPM1A/PP2Calpha, through dephosphorylation of Smad2/3, plays a critical role in terminating TGFbeta signaling. ..
  5. Zhang Y, Feng X, We R, Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. Nature. 1996;383:168-72 pubmed
    ..These results define hMAD-3 and -4 as effectors of the TGF-beta response and demonstrate a function for DPCA-4/hMAD-4 as a tumour suppressor. ..
  6. Suwanabol P, Seedial S, Zhang F, Shi X, Si Y, Liu B, et al. TGF-? and Smad3 modulate PI3K/Akt signaling pathway in vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2012;302:H2211-9 pubmed publisher
    ..Recent studies from our laboratory suggest that in the presence of elevated levels of Smad3, TGF-? stimulates smooth muscle cell (SMC) proliferation...
  7. 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
    ..and TGF-beta led to a potent increase in plasminogen activator inhibitor type 1 transcriptional activity through Smad3 phosphorylation at the linker region...
  8. 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. ..
  9. Costamagna E, Garcia B, Santisteban P. The functional interaction between the paired domain transcription factor Pax8 and Smad3 is involved in transforming growth factor-beta repression of the sodium/iodide symporter gene. J Biol Chem. 2004;279:3439-46 pubmed
    ..inhibitory effect of TGF-beta was partially overcome by inhibitory Smad7 and mimicked by overexpression of either Smad3 or a constitutively activated mutant of TGF-beta receptor I (acALK-5)...

More Information


  1. Gressner O, Lahme B, Rehbein K, Siluschek M, Weiskirchen R, Gressner A. Pharmacological application of caffeine inhibits TGF-beta-stimulated connective tissue growth factor expression in hepatocytes via PPARgamma and SMAD2/3-dependent pathways. J Hepatol. 2008;49:758-67 pubmed publisher
    ..CTGF expression in hepatocytes by stimulation of degradation of the TGF-beta effector SMAD 2, inhibition of SMAD3 phosphorylation and up-regulation of the PPARgamma-receptor...
  2. Tang L, Yamashita M, Coussens N, Tang Y, Wang X, Li C, et al. Ablation of Smurf2 reveals an inhibition in TGF-β signalling through multiple mono-ubiquitination of Smad3. EMBO J. 2011;30:4777-89 pubmed publisher
    ..poly-ubiquitination and degradation, we show that Smurf2 actually induces multiple mono-ubiquitination of Smad3 in vivo...
  3. Qiu P, Ritchie R, Fu Z, Cao D, Cumming J, Miano J, et al. Myocardin enhances Smad3-mediated transforming growth factor-beta1 signaling in a CArG box-independent manner: Smad-binding element is an important cis element for SM22alpha transcription in vivo. Circ Res. 2005;97:983-91 pubmed
    ..Chromatin immunoprecipitation assays reveal that TGF-beta1 induces Smad3 binding to the SM22alpha promoter in vivo...
  4. 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
    ..Interplay between Pur repressor isoforms and Sp1 and Smad coactivators may regulate SMA enhancer output in TGFbeta1-activated myofibroblasts during episodes of wound repair and tissue remodeling. ..
  5. Shi X, Guo L, Seedial S, Si Y, Wang B, Takayama T, et al. TGF-?/Smad3 inhibit vascular smooth muscle cell apoptosis through an autocrine signaling mechanism involving VEGF-A. Cell Death Dis. 2014;5:e1317 pubmed publisher
    We have previously shown that in the presence of elevated Smad3, transforming growth factor-? (TGF-?) transforms from an inhibitor to a stimulant of vascular smooth muscle cell (SMC) proliferation and intimal hyperplasia (IH)...
  6. 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. ..
  7. Song K, Cornelius S, Reiss M, Danielpour D. Insulin-like growth factor-I inhibits transcriptional responses of transforming growth factor-beta by phosphatidylinositol 3-kinase/Akt-dependent suppression of the activation of Smad3 but not Smad2. J Biol Chem. 2003;278:38342-51 pubmed
    ..However, Western blot analysis reveals that IGF-I selectively inhibits the TGF-beta-triggered activation Smad3 but not Smad2, while not altering expression of total Smads 2, 3, or 4...
  8. Yang F, Chung A, Huang X, Lan H. Angiotensin II induces connective tissue growth factor and collagen I expression via transforming growth factor-beta-dependent and -independent Smad pathways: the role of Smad3. Hypertension. 2009;54:877-84 pubmed publisher
    ..cells with deletion of transforming growth factor (TGF)-beta1, overexpression of Smad7, or knockdown of Smad2 or Smad3. We found that Ang II-induced tubular CTGF and collagen I mRNA and protein expressions were regulated positively ..
  9. Li P, Liu P, Chen X, Zhao Y, Ning Y, Yang L, et al. [Effect of small interfering RNA-mediated Smad3 gene silencing on transforming growth factor-beta1-induced bi-directional effects on skin fibroblast proliferation]. Nan Fang Yi Ke Da Xue Xue Bao. 2010;30:690-4 pubmed
    To study the role of Smad3 in transforming growth factor-beta1 (TGF-beta1)-induced bi-directional effects on skin fibroblast proliferation. The Smad3 small interfering (siRNA) plasmid was constructed using a pSUPER vector...
  10. Chung A, Zhang H, Kong Y, Tan J, Huang X, Kopp J, et al. Advanced glycation end-products induce tubular CTGF via TGF-beta-independent Smad3 signaling. J Am Soc Nephrol. 2010;21:249-60 pubmed publisher
    ..Overexpressing Smad7 abolished AGE-induced Smad3 phosphorylation and CTGF expression, demonstrating the necessity for activation of Smad signaling in this process...
  11. Miyazono K. TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000;11:15-22 pubmed
    ..Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types. ..
  12. Watanabe Y, Itoh S, Goto T, Ohnishi E, Inamitsu M, Itoh F, et al. TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad proteins from active participation in TGF-beta signaling. Mol Cell. 2010;37:123-34 pubmed publisher
    ..c-myc expression, whereas specific knockdown of TMEPAI expression prolonged duration of TGF-beta-induced Smad2 and Smad3 phosphorylation and concomitantly potentiated cellular responsiveness to TGF-beta...
  13. Wu G, Glickstein S, Liu W, Fujita T, Li W, Yang Q, et al. The anaphase-promoting complex coordinates initiation of lens differentiation. Mol Biol Cell. 2007;18:1018-29 pubmed
    ..Thus, Cdh1/APC is crucial to the coordination of cell cycle progression and the initiation of lens differentiation through mediating TGF-beta-signaling-induced destruction of SnoN. ..
  14. Kawakatsu M, Kanno S, Gui T, Gai Z, Itoh S, Tanishima H, et al. Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing. Exp Mol Pathol. 2011;90:107-15 pubmed publisher
    b>Smad3 is an intracellular signaling molecule in the transforming growth factor ? (TGF-?) pathway that serves as a regulator of chondrogenesis and osteogenesis...
  15. 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
    ..Two homologs, the receptor-associated Smad3 and the tumor suppressor Smad4/DPC4, synergize to induce ligand-independent TGF-beta activities and are essential ..
  16. Xu J, Oakley J, McGee E. Stage-specific expression of Smad2 and Smad3 during folliculogenesis. Biol Reprod. 2002;66:1571-8 pubmed
    ..Smad2 expression, but not Smad3 expression, returns in luteal cells...
  17. Li G, Wang S, Gelehrter T. Identification of glucocorticoid receptor domains involved in transrepression of transforming growth factor-beta action. J Biol Chem. 2003;278:41779-88 pubmed
    ..activator inhibitor-1 gene transcription by directly targeting the transcriptional activation function of Smad3. To identify the domain(s) in the glucocorticoid receptor involved in this repression, we have examined the ..
  18. Stone J, Holt A, Vuncannon J, Brault J, Tulis D. AMP-activated protein kinase inhibits transforming growth factor-β-mediated vascular smooth muscle cell growth: implications for a Smad-3-dependent mechanism. Am J Physiol Heart Circ Physiol. 2015;309:H1251-9 pubmed publisher
    ..rat VSMCs with the AMPK agonist AICAR significantly decreased TGF-β-mediated activation of synthetic Smad2 and Smad3 and increased inhibitory Smad7...
  19. Guo X, Jose P, Chen S. Response gene to complement 32 interacts with Smad3 to promote epithelial-mesenchymal transition of human renal tubular cells. Am J Physiol Cell Physiol. 2011;300:C1415-21 pubmed publisher
    ..In the present study, we found that RGC-32 function in EMT is associated with Smad3. Coexpression of RGC-32 and Smad3, but not Smad2, induces a higher mesenchymal marker ?-smooth muscle actin (?-SMA)..
  20. 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...
  21. Bao Y, Jiang L, Shi Y, Zou J, Zhao Y, Liu Z. Increased expression of phosphorylated Smad2 and Smad3 in the hippocampus of streptozotocin-induced diabetic rats. Exp Clin Endocrinol Diabetes. 2010;118:47-50 pubmed publisher
    ..01), and phosphorylated Smad3 protein was upregulated at 4 and 8 weeks post streptozotocin induction (p<0...
  22. Yang C, Wang Y, Xu H. Fluoride Regulate Osteoblastic Transforming Growth Factor-?1 Signaling by Mediating Recycling of the Type I Receptor ALK5. PLoS ONE. 2017;12:e0170674 pubmed publisher
    ..Moreover, the expression of Runx2, ALK5 and Smad3 were influenced by SB431542 treatment...
  23. Cheng P, Chang M, Chao C, Lee Y. Hepatitis C viral proteins interact with Smad3 and differentially regulate TGF-beta/Smad3-mediated transcriptional activation. Oncogene. 2004;23:7821-38 pubmed
    ..HCV, only core and nonstructural protein 3 (NS3) physically interact with the MH1 (Mad homology 1) region of the Smad3 and block TGF-beta/Smad3-mediated transcriptional activation through interference with the DNA-binding ability of ..
  24. Ashcroft G, Mills S, Flanders K, Lyakh L, Anzano M, Gilliver S, et al. Role of Smad3 in the hormonal modulation of in vivo wound healing responses. Wound Repair Regen. 2003;11:468-73 pubmed
    b>Smad3 is involved in mediating intracellular signaling by members of the transforming growth factor-beta superfamily and plays a critical role in the cellular proliferation, differentiation, migration, and elaboration of matrix pivotal ..
  25. Tang W, Du L, Sun W, Yu Z, He F, Chen J, et al. Maternal exposure to fine particulate air pollution induces epithelial-to-mesenchymal transition resulting in postnatal pulmonary dysfunction mediated by transforming growth factor-?/Smad3 signaling. Toxicol Lett. 2017;267:11-20 pubmed publisher
    ..These results suggest that EMT up-regulation mediated by the TGF-?/Smad3 pathway plays a role in postnatal pulmonary dysfunction associated with maternal exposure to PM2.5.
  26. Warner D, Bhattacherjee V, Yin X, Singh S, Mukhopadhyay P, Pisano M, et al. Functional interaction between Smad, CREB binding protein, and p68 RNA helicase. Biochem Biophys Res Commun. 2004;324:70-6 pubmed
    ..In order to identify novel Smad 3 binding proteins in developing orofacial tissue, a yeast two hybrid assay was employed in which the MH2 domain of ..
  27. Liu D, Black B, Derynck R. TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev. 2001;15:2950-66 pubmed
    ..Here we show that the TGF-beta intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 ..
  28. Qian Z, Peng Q, Zhang Z, Zhou L, Miao Y. Roles of Smad3 and Smad7 in rat pancreatic stellate cells activated by transforming growth factor-beta 1. Hepatobiliary Pancreat Dis Int. 2010;9:531-6 pubmed
    ..This study aimed to determine the expression of the Smad3 and Smad7 genes in the process of PSC activation, and explore the mechanisms of chronic pancreatitis...
  29. Li Z, Zhou T, Qin Y, Su L, Xu H, Lei F. All-trans retinoic acid attenuates the renal interstitial fibrosis lesion in rats but not by transforming growth factor-?1/Smad3 signaling pathway. Ren Fail. 2013;35:262-7 pubmed publisher
    ..Transforming growth factor-?1 (TGF-?1)/Smad3 signaling pathway is a key signaling pathway which takes part in the progression of renal interstitial fibrosis (..
  30. Suszko M, Antenos M, Balkin D, Woodruff T. Smad3 and Pitx2 cooperate in stimulation of FSHbeta gene transcription. Mol Cell Endocrinol. 2008;281:27-36 pubmed
    ..for FSHbeta gene transcription, as a siRNA-mediated downregulation of Pitx2 protein expression abrogates both Smad3- and activin-mediated stimulation of the FSHbeta promoter...
  31. Zheng Q, Wang Y, Gu X. Wild-type Smad3 gene enhances the osteoblastic differentiation of rat bone marrow-derived mesenchymal stem cells in vitro. J Huazhong Univ Sci Technolog Med Sci. 2005;25:674-8 pubmed
    This study examined the effect of wild-type Smad3 gene on the osteoblastic differentiation of rat bone marrow-derived mesenchymal stem cells in vitro...
  32. Borton A, Frederick J, Datto M, Wang X, Weinstein R. The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res. 2001;16:1754-64 pubmed
    b>Smad3 is a well-characterized intracellular effector of the transforming growth factor beta (TGF-beta) signaling pathway and was implicated recently in the potentiation of vitamin D receptor (VDR)-mediated signaling...
  33. Yang X, Letterio J, Lechleider R, Chen L, Hayman R, Gu H, et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J. 1999;18:1280-91 pubmed
    b>SMAD3 is one of the intracellular mediators that transduces signals from transforming growth factor-beta (TGF-beta) and activin receptors...
  34. Chen J, Yang F, Yu X, Yu Y, Gong Y. Cyclosporine A promotes cell proliferation, collagen and α-smooth muscle actin expressions in rat gingival fibroblasts by Smad3 activation and miR-29b suppression. J Periodontal Res. 2016;51:735-747 pubmed publisher
    Transforming growth factor (TGF)-β/Smad3 signaling promotes tissue fibrosis, and miR-29b is a downstream inhibitor of TGF-β/Smad3-mediated fibrosis, both of which may be involved in the pathogenesis of cyclosporine A-induced ..
  35. Wu D, Lei H, Wang J, Zhang C, Feng H, Fu F, et al. CTRP3 attenuates post-infarct cardiac fibrosis by targeting Smad3 activation and inhibiting myofibroblast differentiation. J Mol Med (Berl). 2015;93:1311-25 pubmed publisher
    ..CTRP3 also attenuated TGF-β1-induced Smad3 phosphorylation, nuclear translocation, and interaction with p300...
  36. Yang N, Dang S, Shi J, Wu F, Li M, Zhang X, et al. Caffeic acid phenethyl ester attenuates liver fibrosis via inhibition of TGF-?1/Smad3 pathway and induction of autophagy pathway. Biochem Biophys Res Commun. 2017;486:22-28 pubmed publisher
    ..of HSCs as determined by the expression alternation of transforming growth factor (TGF)-?1, phosphorylated Smad3 (p-Smad3), collage I, ?-smooth muscle actin (?-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of ..
  37. Bai G, Yan G, Wang G, Wan P, Zhang R. Anti-hepatic fibrosis effects of a novel turtle shell decoction by inhibiting hepatic stellate cell proliferation and blocking TGF-?1/Smad signaling pathway in rats. Oncol Rep. 2016;36:2902-2910 pubmed publisher
    ..Moreover, the NTSD treatment significantly decreased the transforming growth factor beta 1 (TGF-?1) and Smad3 gene expression and increased inhibitory Smad7 gene expression in liver tissues of HF rats, suggesting that NTSD ..
  38. Uchiyama Y, Guttapalli A, Gajghate S, Mochida J, Shapiro I, Risbud M. SMAD3 functions as a transcriptional repressor of acid-sensing ion channel 3 (ASIC3) in nucleus pulposus cells of the intervertebral disc. J Bone Miner Res. 2008;23:1619-28 pubmed publisher
    ..the nucleus pulposus cells were treated with TGFbeta or co-transfected with the constitutively active ALK5 or a smad3 construct. On the other hand, co-transfection of dominant negative smad3 or smad7 restored ASIC3 promoter activity...
  39. Thuault S, Tan E, Peinado H, Cano A, Heldin C, Moustakas A. HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem. 2008;283:33437-46 pubmed publisher
    ..The data propose that HMGA2 acts in a gene-specific manner to orchestrate the transcriptional network necessary for the EMT program. ..
  40. Chen H, Rud J, Lin K, Xu L. Nuclear targeting of transforming growth factor-beta-activated Smad complexes. J Biol Chem. 2005;280:21329-36 pubmed
    Upon stimulation by the transforming growth factor beta (TGF-beta), Smad2 and Smad3 are phosphorylated at their C termini and assemble into stable heteromeric complexes with Smad4...
  41. 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
    ..Therefore, sustained selective inhibition of PKC?II in a post-MI HF rat model improves cardiac function and is associated with inhibition of pathological myocardial remodelling. ..
  42. Suszko M, Balkin D, Chen Y, Woodruff T. Smad3 mediates activin-induced transcription of follicle-stimulating hormone beta-subunit gene. Mol Endocrinol. 2005;19:1849-58 pubmed
    ..Activin signals through a pathway that involves the activation of the transcriptional coregulators Smad2 and Smad3. Previous work from our laboratory demonstrated that Smad3, and not Smad2, is sufficient for stimulation of the ..
  43. Symonds D, Tomic D, Borgeest C, McGee E, Flaws J. Smad 3 regulates proliferation of the mouse ovarian surface epithelium. Anat Rec A Discov Mol Cell Evol Biol. 2003;273:681-6 pubmed
    b>Smad 3 is a signaling intermediate for the transforming growth factor beta (TGFbeta) family; however, little is known about the role this protein plays in the regulation of the ovarian surface epithelium (OSE)...
  44. Liu G, Ding W, Neiman J, Mulder K. Requirement of Smad3 and CREB-1 in mediating transforming growth factor-beta (TGF beta) induction of TGF beta 3 secretion. J Biol Chem. 2006;281:29479-90 pubmed
    ..Electrophoresis mobility supershift assays indicated that CRE-binding protein 1 (CREB1) and Smad3 were the major components present in this TGFbeta-inducible complex...
  45. Zhang H, Cui Y, Li K, Yang B, Liu X, Zhang D, et al. Glutamine protects cardiomyocytes from hypoxia/reoxygenation injury under high glucose conditions through inhibition of the transforming growth factor-β1-Smad3 pathway. Arch Biochem Biophys. 2016;596:43-50 pubmed publisher
    Activation of transforming growth factor-β1 (TGF-β1)-Smad3 pathway aggravates myocardial ischemia/reperfusion injury (IRI)...
  46. Wu T, Chen J, Xiao T, Shu X, Xu H, Yang L, et al. Qinggan Huoxue Recipe suppresses epithelial-to-mesenchymal transition in alcoholic liver fibrosis through TGF-?1/Smad signaling pathway. World J Gastroenterol. 2016;22:4695-706 pubmed publisher
    ..on molecules associated with the transforming growth factor (TGF)-?1/Smad signaling pathway, including TGF-?1, Smad3, snail, occludin, ZO-1 and claudin, was also examined...
  47. Wang X, Lai R, Su X, Chen G, Liang Z. Edaravone attenuates lipopolysaccharide-induced acute respiratory distress syndrome associated early pulmonary fibrosis via amelioration of oxidative stress and transforming growth factor-?1/Smad3 signaling. Biochem Biophys Res Commun. 2018;495:706-712 pubmed publisher
    ..I levels, stimulated myofibroblast differentiation and induced expression of TGF-?1 and activation of TGF-?1/Smad3 signaling as early as day 7 after LPS injection...
  48. Wei X, Liu Y, Li Q, Yan L, Hu B, Pan C, et al. Treatment with cardiotonic pills(®) after ischemia-reperfusion ameliorates myocardial fibrosis in rats. Microcirculation. 2013;20:17-29 pubmed publisher
    ..The expression of MCP-1, RP S19, TGF-?1, P-Smad3, Smad4, MMP-9 and ?-SMA, and the infiltration of leukocytes were examined...
  49. Huang X, Wen D, Zhang M, Xie Q, Ma L, Guan Y, et al. Sirt1 activation ameliorates renal fibrosis by inhibiting the TGF-?/Smad3 pathway. J Cell Biochem. 2014;115:996-1005 pubmed publisher
    TGF-? signaling plays an important role in the pathogenesis and progression of chronic kidney disease (CKD). Smad3, a transcription factor, is a critical fibrogenic mediator of TGF-?...
  50. Guo X, Waddell D, Wang W, Wang Z, Liberati N, Yong S, et al. Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling. Oncogene. 2008;27:7235-47 pubmed publisher
    ..of cellular activities primarily through a signaling cascade mediated by two key transcription factors, Smad2 and Smad3. Numerous regulatory mechanisms exist to control the activity of Smad3, thereby modulating the strength and ..
  51. Song K, Wang H, Krebs T, Danielpour D. Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation. EMBO J. 2006;25:58-69 pubmed
    ..Insulin-like growth factor-I inhibits transforming growth factor-beta (TGF-beta) signaling by blocking activation of Smad3 (S3), via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent pathway...
  52. Harada J, Kokura K, Kanei Ishii C, Nomura T, Khan M, Kim Y, et al. Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation. J Biol Chem. 2003;278:38998-9005 pubmed
    ..The HIPK2 co-repressor activity may be regulated by an uncharacterized HIPK2 kinase. These results indicate that HIPK2, together with c-Ski, plays an important role in the negative regulation of BMP-induced transcriptional activation. ..
  53. Ellis L, Warner D, Greene R, Pisano M. Interaction of Smads with collagen types I, III, and V. Biochem Biophys Res Commun. 2003;310:1117-23 pubmed
    ..we have identified three types of collagens (types I, III, and V) that are capable of binding to the MH2 domain of Smad 3. These interactions were confirmed by glutathione S-transferase (GST) pull-down assays in which the MH2 domain of ..