Smad3

Summary

Gene Symbol: Smad3
Description: SMAD family member 3
Alias: AU022421, Madh3, mothers against decapentaplegic homolog 3, MAD homolog 3, Smad 3, mMad3, mad3, mothers against DPP homolog 3
Species: mouse
Products:     Smad3

Top Publications

  1. Latella G, Vetuschi A, Sferra R, Catitti V, D Angelo A, Zanninelli G, et al. Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine-induced hepatic fibrosis in mice. Liver Int. 2009;29:997-1009 pubmed publisher
    ..Transforming growth factor-beta (TGF-beta)/Smad3 signalling plays a central role in tissue fibrogenesis, acting as a potent stimulus of ECM accumulation...
  2. Wang A, Ziyadeh F, Lee E, Pyagay P, Sung S, Sheardown S, et al. Interference with TGF-beta signaling by Smad3-knockout in mice limits diabetic glomerulosclerosis without affecting albuminuria. Am J Physiol Renal Physiol. 2007;293:F1657-65 pubmed
    ..To isolate the contribution of one of the signaling pathways of TGF-beta, the Smad3 gene in the mouse was knocked out at exons 2 and 3, and the effect was studied in streptozotocin (STZ)-induced ..
  3. Velden J, Alcorn J, Guala A, Badura E, Janssen Heininger Y. c-Jun N-terminal kinase 1 promotes transforming growth factor-?1-induced epithelial-to-mesenchymal transition via control of linker phosphorylation and transcriptional activity of Smad3. Am J Respir Cell Mol Biol. 2011;44:571-81 pubmed publisher
    ..via Smad complexes, the goal of the present study was to determine the impact of JNK1 on phosphorylation of Smad3 and Smad3-dependent transcriptional responses in lung epithelial cells...
  4. Xavier S, Niranjan T, Krick S, Zhang T, Ju W, Shaw A, et al. TbetaRI independently activates Smad- and CD2AP-dependent pathways in podocytes. J Am Soc Nephrol. 2009;20:2127-37 pubmed publisher
    ..TGF-beta promotes proapoptotic signaling mediated by Smad3 but also activates prosurvival pathways such as phosphoinositide-3 kinase (PI3K)/AKT; the latter requires the CD2-..
  5. Meng X, Huang X, Chung A, Qin W, Shao X, Igarashi P, et al. Smad2 protects against TGF-beta/Smad3-mediated renal fibrosis. J Am Soc Nephrol. 2010;21:1477-87 pubmed publisher
    Smad2 and Smad3 interact and mediate TGF-beta signaling. Although Smad3 promotes fibrosis, the role of Smad2 in fibrogenesis is largely unknown...
  6. Sartori R, Milan G, Patron M, Mammucari C, Blaauw B, Abraham R, et al. Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Cell Physiol. 2009;296:C1248-57 pubmed publisher
    ..Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF-beta and induce an atrophy program that is muscle RING-..
  7. Tone Y, Furuuchi K, Kojima Y, Tykocinski M, Greene M, Tone M. Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat Immunol. 2008;9:194-202 pubmed
    ..The transcription factors Smad3 and NFAT are required for activity of this Foxp3 enhancer, and both factors are essential for histone acetylation ..
  8. Trotta R, Dal Col J, Yu J, Ciarlariello D, Thomas B, Zhang X, et al. TGF-beta utilizes SMAD3 to inhibit CD16-mediated IFN-gamma production and antibody-dependent cellular cytotoxicity in human NK cells. J Immunol. 2008;181:3784-92 pubmed
    ..TGF-beta treatment induced SMAD3 phosphorylation, and ectopic overexpression of SMAD3 resulted in a significant decrease in IFN-gamma gene ..
  9. Le A, Cho J, Miller M, McElwain S, Golgotiu K, Broide D. Inhibition of allergen-induced airway remodeling in Smad 3-deficient mice. J Immunol. 2007;178:7310-6 pubmed
    Intracellular signaling pathways that converge on Smad 3 are used by both TGF-beta and activin A, key cytokines implicated in the process of fibrogenesis...

More Information

Publications61

  1. Carlson M, Hsu M, Conboy I. Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells. Nature. 2008;454:528-32 pubmed publisher
    ..Thus a balance between endogenous pSmad3 and active Notch controls the regenerative competence of muscle stem cells, and deregulation of this balance in the old muscle microniche interferes with regeneration. ..
  2. Guzman Ayala M, Lee K, Mavrakis K, Goggolidou P, Norris D, Episkopou V. Graded Smad2/3 activation is converted directly into levels of target gene expression in embryonic stem cells. PLoS ONE. 2009;4:e4268 pubmed publisher
    ..The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFbeta signalling: they are activated by receptors, enter the ..
  3. Mullen A, Orlando D, Newman J, Lovén J, Kumar R, Bilodeau S, et al. Master transcription factors determine cell-type-specific responses to TGF-? signaling. Cell. 2011;147:565-76 pubmed publisher
    Transforming growth factor beta (TGF-?) signaling, mediated through the transcription factors Smad2 and Smad3 (Smad2/3), directs different responses in different cell types...
  4. Hamby M, Hewett J, Hewett S. Smad3-dependent signaling underlies the TGF-?1-mediated enhancement in astrocytic iNOS expression. Glia. 2010;58:1282-91 pubmed publisher
    ..Consistent with ALK5 signaling, Smad3 accumulated in the nucleus of astrocytes as early as 30 min after TGF-beta1 (3 ng/mL) treatment and persisted upto ..
  5. Falk S, Wurdak H, Ittner L, Ille F, Sumara G, Schmid M, et al. Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion. Cell Stem Cell. 2008;2:472-83 pubmed publisher
    ..Thus, TGF-beta signaling controls the size of a specific brain area, the dorsal midbrain, by antagonizing canonical Wnt signaling and negatively regulating self-renewal of neuroepithelial stem cells. ..
  6. Deane N, Manning H, Foutch A, Washington M, Aronow B, Aronow B, et al. Targeted imaging of colonic tumors in smad3-/- mice discriminates cancer and inflammation. Mol Cancer Res. 2007;5:341-9 pubmed
    ..NIR-conPK11195 localized and was retained in colonic adenomas and carcinomas in Smad3(-/-) mice but not in non-neoplastic hamartomas or chronically inflamed colonic tissue...
  7. Chen H, Sun J, Buckley S, Chen C, Warburton D, Wang X, et al. Abnormal mouse lung alveolarization caused by Smad3 deficiency is a developmental antecedent of centrilobular emphysema. Am J Physiol Lung Cell Mol Physiol. 2005;288:L683-91 pubmed
    ..b>Smad3 is a major downstream signal transducer in the TGF-beta pathway from the cell membrane to the nucleus...
  8. Vallejo Illarramendi A, Zang K, Reichardt L. Focal adhesion kinase is required for neural crest cell morphogenesis during mouse cardiovascular development. J Clin Invest. 2009;119:2218-30 pubmed publisher
    ..Our results indicate that FAK plays an essential role in cardiac outflow tract development by promoting the activation of molecules such as Crkl and Erk1/2...
  9. Li J, Qu X, Yao J, Caruana G, Ricardo S, Yamamoto Y, et al. Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes. 2010;59:2612-24 pubmed publisher
    ..Phosphorylated Smad3 was detected by immunoprecipitation/Western blotting and confocal microscopy...
  10. Jenkins B, Grail D, Nheu T, Najdovska M, Wang B, Waring P, et al. Hyperactivation of Stat3 in gp130 mutant mice promotes gastric hyperproliferation and desensitizes TGF-beta signaling. Nat Med. 2005;11:845-52 pubmed
  11. Nolting J, Daniel C, Reuter S, Stuelten C, Li P, Sucov H, et al. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. J Exp Med. 2009;206:2131-9 pubmed publisher
    ..The latter effect depended on the RA receptor alpha (RAR alpha) but did not require Smad3, despite the fact that RA enhanced Smad3 expression...
  12. Maggio Price L, Treuting P, Zeng W, Tsang M, Bielefeldt Ohmann H, Iritani B. Helicobacter infection is required for inflammation and colon cancer in SMAD3-deficient mice. Cancer Res. 2006;66:828-38 pubmed
    ..Although others have reported that mice deficient in the TGF-beta signaling molecule SMAD3 develop colon cancer, we found that SMAD3-deficient mice maintained free of the Gram-negative enterohepatic ..
  13. 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. ..
  14. Ju W, Ogawa A, Heyer J, Nierhof D, Yu L, Kucherlapati R, et al. Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. Mol Cell Biol. 2006;26:654-67 pubmed
    Smad family proteins Smad2 and Smad3 are activated by transforming growth factor beta (TGF-beta)/activin/nodal receptors and mediate transcriptional regulation...
  15. Kuratomi G, Komuro A, Goto K, Shinozaki M, Miyazawa K, Miyazono K, et al. NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor. Biochem J. 2005;386:461-70 pubmed
    ..TGF-beta-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), ..
  16. Stramer B, Austin J, Roberts A, Fini M. Selective reduction of fibrotic markers in repairing corneas of mice deficient in Smad3. J Cell Physiol. 2005;203:226-32 pubmed
    ..Expression of fibrotic markers in repairing cutaneous wounds is reduced in mice lacking Smad3, a downstream cytoplasmic mediator of TGF-beta signaling (Ashcroft et al., 1999, Nat Cell Biol 1(5):260-266)...
  17. Lin H, Lee J, Yadav H, Kamaraju A, Liu E, Zhigang D, et al. Transforming growth factor-beta/Smad3 signaling regulates insulin gene transcription and pancreatic islet beta-cell function. J Biol Chem. 2009;284:12246-57 pubmed publisher
    ..We identify insulin as a TGF-beta target gene and show that the TGF-beta signaling effector Smad3 occupies the insulin gene promoter and represses insulin gene transcription...
  18. Maggio Price L, Treuting P, Bielefeldt Ohmann H, Seamons A, Drivdahl R, Zeng W, et al. Bacterial infection of Smad3/Rag2 double-null mice with transforming growth factor-beta dysregulation as a model for studying inflammation-associated colon cancer. Am J Pathol. 2009;174:317-29 pubmed publisher
    ..Similarly, mice deficient in the transforming growth factor-beta signaling molecule, Smad3, develop colon cancer, but only after a bacterial trigger occurs, resulting in chronic inflammation...
  19. Dennler S, Andre J, Alexaki I, Li A, Magnaldo T, Ten Dijke P, et al. Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo. Cancer Res. 2007;67:6981-6 pubmed
    ..In transgenic mice overexpressing TGF-beta1 in the skin, Gli1 and Gli2 expression is also elevated and depends on Smad3. In pancreatic adenocarcinoma cell lines resistant to Hh inhibition, pharmacologic blockade of TGF-beta signaling ..
  20. Arany P, Flanders K, Kobayashi T, Kuo C, Stuelten C, Desai K, et al. Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure. Proc Natl Acad Sci U S A. 2006;103:9250-5 pubmed
    The loss of TGFbeta or its downstream mediator, Smad3, key players in tissue repair, accelerates closure of incisional wounds in mice...
  21. Wang G, Matsuura I, He D, Liu F. Transforming growth factor-{beta}-inducible phosphorylation of Smad3. J Biol Chem. 2009;284:9663-73 pubmed publisher
    ..Upon TGF-beta treatment, the highly homologous Smad2 and Smad3 are phosphorylated by the TGF-beta receptor at the SSXS motif in the C-terminal tail...
  22. Sun Q, Zhang Y, Yang G, Chen X, Zhang Y, Cao G, et al. Transforming growth factor-beta-regulated miR-24 promotes skeletal muscle differentiation. Nucleic Acids Res. 2008;36:2690-9 pubmed publisher
    ..blot analysis, we showed that TGF-beta1 repressed miR-24 transcription which was dependent on the presence of Smad3 and a Smads binding site in the promoter region of miR-24...
  23. Xu L, Kitani A, Stuelten C, McGrady G, Fuss I, Strober W. Positive and negative transcriptional regulation of the Foxp3 gene is mediated by access and binding of the Smad3 protein to enhancer I. Immunity. 2010;33:313-25 pubmed publisher
    ..were here shown to be related processes involving modifications of baseline (TGF-β-induced) phosphorylated Smad3 (pSmad3) binding to a conserved enhancer region (enhancer I)...
  24. Murashima Suginami A, Takahashi K, Sakata T, Tsukamoto H, Sugai M, Yanagita M, et al. Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse. Biochem Biophys Res Commun. 2008;369:1012-6 pubmed publisher
    ..Based upon these results, we conclude that enhanced BMP signaling results in supernumerary teeth and BMP signaling was modulated by Wnt signaling in the USAG-1 deficient mouse model. ..
  25. Kang J, Alliston T, Delston R, Derynck R. Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3. EMBO J. 2005;24:2543-55 pubmed
    ..factor-beta (TGF-beta) inhibits osteoblast differentiation through inhibition of the function of Runx2 (Cbfa1) by Smad3. The mechanism through which TGF-beta/Smad3 inhibits Runx2 function has not been characterized...
  26. Baburajendran N, Palasingam P, Narasimhan K, Sun W, Prabhakar S, Jauch R, et al. Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-beta effectors. Nucleic Acids Res. 2010;38:3477-88 pubmed publisher
    ..On the contrary, the TGF-beta-activated Smad3 triggers strikingly different programs such as mesodermal differentiation in early development...
  27. Alejandre Alcazar M, Michiels Corsten M, Vicencio A, Reiss I, Ryu J, de Krijger R, et al. TGF-beta signaling is dynamically regulated during the alveolarization of rodent and human lungs. Dev Dyn. 2008;237:259-69 pubmed
    ..of the TGF-beta receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3, Smad4, Smad6, and Smad7 were noted as mouse and human lungs progressed through the canalicular, saccular, and ..
  28. Gao S, Alarcon C, Sapkota G, Rahman S, Chen P, Goerner N, et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell. 2009;36:457-68 pubmed publisher
    TGF-beta induces phosphorylation of the transcription factors Smad2 and Smad3 at the C terminus as well as at an interdomain linker region...
  29. Huang X, Chung A, Yang F, Yue W, Deng C, Lau C, et al. Smad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling. Hypertension. 2010;55:1165-71 pubmed publisher
    Although Smad3 is a key mediator of fibrosis, the functional role of Smad3 in hypertensive cardiovascular disease remains unclear...
  30. Chung A, Huang X, Meng X, Lan H. miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. J Am Soc Nephrol. 2010;21:1317-25 pubmed publisher
    TGF-beta/Smad3 promotes renal fibrosis, but the mechanisms that regulate profibrotic genes remain unclear. We hypothesized that miR-192, a microRNA expressed in the kidney may mediate renal fibrosis in a Smad3-dependent manner...
  31. Funaba M, Nakaya K, Ikeda T, Murakami M, Tsuchida K, Sugino H. Requirement of Smad3 for mast cell growth. Cell Immunol. 2006;240:47-52 pubmed
    ..Doubling time of BMMC from Smad3-null mice was longer than that from wild-type (WT) mice, and the differences tended to be larger with time of ..
  32. Ge X, McFarlane C, Vajjala A, Lokireddy S, Ng Z, Tan C, et al. Smad3 signaling is required for satellite cell function and myogenic differentiation of myoblasts. Cell Res. 2011;21:1591-604 pubmed publisher
    ..Both growth factors have been shown to signal through a Smad3-dependent pathway. However to date, the role of Smad3 in muscle growth and differentiation is not investigated...
  33. Takimoto T, Wakabayashi Y, Sekiya T, Inoue N, Morita R, Ichiyama K, et al. Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. J Immunol. 2010;185:842-55 pubmed publisher
    ..TGF-beta plays a pivotal role in immune regulation, the roles of its downstream transcription factors, Smad2 and Smad3, have not been fully clarified...
  34. Tan N, Michalik L, Di Poï N, Ng C, Mermod N, Roberts A, et al. Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression. EMBO J. 2004;23:4211-21 pubmed
    ..Whereas conditions that mimic the initial inflammatory events stimulate PPARbeta/delta expression, TGF-beta1/Smad3 suppresses this inflammation-induced PPARbeta/delta transcription, as seen in the late re-epithelialization/..
  35. Tapia Gonzalez S, Giraldez Perez R, Cuartero M, Casarejos M, Mena M, Wang X, et al. Dopamine and ?-synuclein dysfunction in Smad3 null mice. Mol Neurodegener. 2011;6:72 pubmed publisher
    ..We have examined the mesostriatal system in adult mice deficient in Smad3, a molecule involved in the intracellular TGF-?1 signalling cascade...
  36. Wang Y, Symes A. Smad3 deficiency reduces neurogenesis in adult mice. J Mol Neurosci. 2010;41:383-96 pubmed publisher
    Transforming growth factor-beta signaling through Smad3 inhibits cell proliferation in many cell types...
  37. Liu Z, Huang X, Lan H. Smad3 mediates ANG II-induced hypertensive kidney disease in mice. Am J Physiol Renal Physiol. 2012;302:F986-97 pubmed publisher
    Although Smad3 is a key mediator for fibrosis, its functional role and mechanisms in hypertensive nephropathy remain largely unclear...
  38. Latella G, Vetuschi A, Sferra R, Zanninelli G, D Angelo A, Catitti V, et al. Smad3 loss confers resistance to the development of trinitrobenzene sulfonic acid-induced colorectal fibrosis. Eur J Clin Invest. 2009;39:145-56 pubmed publisher
    Transforming growth factor-beta (TGF-beta)/Smad3 signalling plays a central role in tissue fibrogenesis, acting as a potent stimulus of extracellular matrix (ECM) protein accumulation...
  39. 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...
  40. Matsuura I, Denissova N, Wang G, He D, Long J, Liu F. Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature. 2004;430:226-31 pubmed
    Transforming growth factor-beta (TGF-beta) potently inhibits cell cycle progression at the G1 phase. Smad3 has a key function in mediating the TGF-beta growth-inhibitory response...
  41. Zhao J, Shi W, Wang Y, Chen H, Bringas P, Datto M, et al. Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol. 2002;282:L585-93 pubmed
    Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung fibrogenesis. Smad3 was identified in the pathway for transducing TGF-beta signals from the cell membrane to the nucleus...
  42. Cui X, Chai Y, Chen J, Yamamoto T, Ito Y, Bringas P, et al. TGF-beta3-dependent SMAD2 phosphorylation and inhibition of MEE proliferation during palatal fusion. Dev Dyn. 2003;227:387-94 pubmed
    ..SMAD2 and SMAD3 were both present in the MEE, whereas SMAD2 was the only one phosphorylated during palatal fusion...
  43. 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. ..
  44. Yokozeki M, Afanador E, Nishi M, Kaneko K, Shimokawa H, Yokote K, et al. Smad3 is required for enamel biomineralization. Biochem Biophys Res Commun. 2003;305:684-90 pubmed
    b>Smad3 is an intracellular signaling molecule that mediates the signal from transforming growth factor-beta (TGF-beta) and activin receptors...
  45. Zhu Y, Richardson J, Parada L, Graff J. Smad3 mutant mice develop metastatic colorectal cancer. Cell. 1998;94:703-14 pubmed
    ..TGFbeta transduces its signal to the interior of the cell via Smad2, Smad3, and Smad4. We report the cloning and targeted disruption of the mouse Smad3 gene...
  46. McKarns S, Schwartz R, Kaminski N. Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J Immunol. 2004;172:4275-84 pubmed
    ..We used Smad3(-/-) mice to investigate a role for Smad3 in IL-2 production and proliferation in T cells...
  47. Flanders K, Major C, Arabshahi A, Aburime E, Okada M, Fujii M, et al. Interference with transforming growth factor-beta/ Smad3 signaling results in accelerated healing of wounds in previously irradiated skin. Am J Pathol. 2003;163:2247-57 pubmed
    ..We previously showed that epithelialization of incisional wounds is accelerated in mice null for Smad3, a key cytoplasmic mediator of TGF-beta signaling...
  48. Sato M, Muragaki Y, Saika S, Roberts A, Ooshima A. Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest. 2003;112:1486-94 pubmed
    ..We now show that mice lacking Smad3 (Smad3ex8/ex8), a key signaling intermediate downstream of the TGF-beta receptors, are protected against ..
  49. 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...
  50. Datto M, Frederick J, Pan L, Borton A, Zhuang Y, Wang X. Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. Mol Cell Biol. 1999;19:2495-504 pubmed
    ..To discern the in vivo functions of one of these Smads, Smad3, we generated mice harboring a targeted disruption of this gene...
  51. Sowa H, Kaji H, Hendy G, Canaff L, Komori T, Sugimoto T, et al. Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2. J Biol Chem. 2004;279:40267-75 pubmed
    ..In the osteoblast MC3T3-E1 cells, transforming growth factor-beta and its signaling molecule, Smad3, negatively regulated Runx2 transcriptional activity...
  52. Tokumasa A, Katsuno T, Tanaga T, Yokote K, Saito Y, Suzuki Y. Reduction of Smad3 accelerates re-epithelialization in a murine model of colitis. Biochem Biophys Res Commun. 2004;317:377-83 pubmed
    To determine the role of Smad3 in re-epithelialization and inflammation, experimental colitis was induced in Smad3 heterozygous mice and their wild-type littermates by single intrarectal administration of 2,4,6-trinitrobenzene sulfonic ..