Smad7

Summary

Gene Symbol: Smad7
Description: SMAD family member 7
Alias: Madh7, mothers against decapentaplegic homolog 7, MAD homolog 7, MAD homolog 8, SMAD 7, madh8, mothers against DPP homolog 7, mothers against DPP homolog 8, mothers against decapentaplegic homolog 8
Species: mouse
Products:     Smad7

Top Publications

  1. Dooley S, Hamzavi J, Ciuclan L, Godoy P, Ilkavets I, Ehnert S, et al. Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage. Gastroenterology. 2008;135:642-59 pubmed publisher
    ..Furthermore, a transgenic mouse model was used to determine the outcome of hepatocyte-specific Smad7 expression on fibrogenesis following CCl(4)-dependent damage...
  2. Smart N, Apelqvist A, Gu X, Harmon E, Topper J, Macdonald R, et al. Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus. PLoS Biol. 2006;4:e39 pubmed
    ..Here we describe a conditional system for expressing Smad7, a potent inhibitor of TGF-beta signaling, to identify distinct roles for this pathway in adult and embryonic beta ..
  3. Chen H, Huang X, Wang W, Li J, Heuchel R, Chung A, et al. The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential. Diabetes. 2011;60:590-601 pubmed publisher
    ..a downstream mediator of transforming growth factor-β (TGF-β) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear...
  4. Fantini M, Becker C, Monteleone G, Pallone F, Galle P, Neurath M. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J Immunol. 2004;172:5149-53 pubmed
    ..Similarly, TGF-beta induced Foxp3 in human CD4(+)CD25(-) T cells. Moreover, we show that the inhibitory Smad7 protein that is normally induced by TGF-beta and limits TGF-beta signaling, is strongly down-regulated by Foxp3 at ..
  5. Chen Q, Chen H, Zheng D, Kuang C, Fang H, Zou B, et al. Smad7 is required for the development and function of the heart. J Biol Chem. 2009;284:292-300 pubmed publisher
    ..These effects are largely mediated by Smad proteins. Smad7 is a negative regulator for the signaling of TGF-beta family members...
  6. Souchelnytskyi S, Nakayama T, Nakao A, Moren A, Heldin C, Christian J, et al. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. J Biol Chem. 1998;273:25364-70 pubmed
    ..b>Smad7, for example, binds to and inhibits signaling downstream of TGF-beta receptors...
  7. Nagano Y, Mavrakis K, Lee K, Fujii T, Koinuma D, Sase H, et al. Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling. J Biol Chem. 2007;282:20492-501 pubmed
    ..Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress ..
  8. Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, et al. Smad6 inhibits signalling by the TGF-beta superfamily. Nature. 1997;389:622-6 pubmed
    ..These data indicate that signals of the TGF-beta superfamily are regulated both positively and negatively by members of the SMAD family. ..
  9. Gruber T, Hinterleitner R, Hermann Kleiter N, Meisel M, Kleiter I, Wang C, et al. Cbl-b mediates TGFβ sensitivity by downregulating inhibitory SMAD7 in primary T cells. J Mol Cell Biol. 2013;5:358-68 pubmed publisher
    ..This study shows that SMAD7, an established negative regulator of TGFβ receptor (TGFβR) signaling, is a key downstream effector target of ..
  10. Fukasawa H, Yamamoto T, Togawa A, Ohashi N, Fujigaki Y, Oda T, et al. Down-regulation of Smad7 expression by ubiquitin-dependent degradation contributes to renal fibrosis in obstructive nephropathy in mice. Proc Natl Acad Sci U S A. 2004;101:8687-92 pubmed
    ..of Smad proteins have been identified: receptor-regulated Smad2 and Smad3, common partner Smad4, and inhibitory Smad7 (part of a negative-feedback loop)...

Detail Information

Publications62

  1. Dooley S, Hamzavi J, Ciuclan L, Godoy P, Ilkavets I, Ehnert S, et al. Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage. Gastroenterology. 2008;135:642-59 pubmed publisher
    ..Furthermore, a transgenic mouse model was used to determine the outcome of hepatocyte-specific Smad7 expression on fibrogenesis following CCl(4)-dependent damage...
  2. Smart N, Apelqvist A, Gu X, Harmon E, Topper J, Macdonald R, et al. Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus. PLoS Biol. 2006;4:e39 pubmed
    ..Here we describe a conditional system for expressing Smad7, a potent inhibitor of TGF-beta signaling, to identify distinct roles for this pathway in adult and embryonic beta ..
  3. Chen H, Huang X, Wang W, Li J, Heuchel R, Chung A, et al. The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential. Diabetes. 2011;60:590-601 pubmed publisher
    ..a downstream mediator of transforming growth factor-β (TGF-β) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear...
  4. Fantini M, Becker C, Monteleone G, Pallone F, Galle P, Neurath M. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J Immunol. 2004;172:5149-53 pubmed
    ..Similarly, TGF-beta induced Foxp3 in human CD4(+)CD25(-) T cells. Moreover, we show that the inhibitory Smad7 protein that is normally induced by TGF-beta and limits TGF-beta signaling, is strongly down-regulated by Foxp3 at ..
  5. Chen Q, Chen H, Zheng D, Kuang C, Fang H, Zou B, et al. Smad7 is required for the development and function of the heart. J Biol Chem. 2009;284:292-300 pubmed publisher
    ..These effects are largely mediated by Smad proteins. Smad7 is a negative regulator for the signaling of TGF-beta family members...
  6. Souchelnytskyi S, Nakayama T, Nakao A, Moren A, Heldin C, Christian J, et al. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. J Biol Chem. 1998;273:25364-70 pubmed
    ..b>Smad7, for example, binds to and inhibits signaling downstream of TGF-beta receptors...
  7. Nagano Y, Mavrakis K, Lee K, Fujii T, Koinuma D, Sase H, et al. Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling. J Biol Chem. 2007;282:20492-501 pubmed
    ..Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress ..
  8. Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, et al. Smad6 inhibits signalling by the TGF-beta superfamily. Nature. 1997;389:622-6 pubmed
    ..These data indicate that signals of the TGF-beta superfamily are regulated both positively and negatively by members of the SMAD family. ..
  9. Gruber T, Hinterleitner R, Hermann Kleiter N, Meisel M, Kleiter I, Wang C, et al. Cbl-b mediates TGFβ sensitivity by downregulating inhibitory SMAD7 in primary T cells. J Mol Cell Biol. 2013;5:358-68 pubmed publisher
    ..This study shows that SMAD7, an established negative regulator of TGFβ receptor (TGFβR) signaling, is a key downstream effector target of ..
  10. Fukasawa H, Yamamoto T, Togawa A, Ohashi N, Fujigaki Y, Oda T, et al. Down-regulation of Smad7 expression by ubiquitin-dependent degradation contributes to renal fibrosis in obstructive nephropathy in mice. Proc Natl Acad Sci U S A. 2004;101:8687-92 pubmed
    ..of Smad proteins have been identified: receptor-regulated Smad2 and Smad3, common partner Smad4, and inhibitory Smad7 (part of a negative-feedback loop)...
  11. Chung A, Huang X, Zhou L, Heuchel R, Lai K, Lan H. Disruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice. Nephrol Dial Transplant. 2009;24:1443-54 pubmed publisher
    The present study tested the hypothesis that disruption of Smad7 function may accelerate renal fibrosis and inflammation.
  12. Nakao A, Afrakhte M, Moren A, Nakayama T, Christian J, Heuchel R, et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature. 1997;389:631-5 pubmed
    ..Here we report the identification of Smad7, which is related to Smad6...
  13. Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, et al. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003;22:6458-70 pubmed
    ..Arkadia physically interacts with inhibitory Smad, Smad7, and induces its poly-ubiquitination and degradation...
  14. Liu X, Chen Q, Kuang C, Zhang M, Ruan Y, Xu Z, et al. A 4.3 kb Smad7 promoter is able to specify gene expression during mouse development. Biochim Biophys Acta. 2007;1769:149-52 pubmed
    ..b>Smad7 is an inhibitory Smad protein that specifically antagonizes TGF-beta and activin signaling...
  15. Warner D, Roberts E, Greene R, Pisano M. Identification of novel Smad binding proteins. Biochem Biophys Res Commun. 2003;312:1185-90 pubmed
    ..The identification of these proteins as Smad binding partners allows exploration of new mechanisms whereby TGFbeta signaling may be regulated, and reveals additional potential interactions with other signaling pathways. ..
  16. Schiffer M, Schiffer L, Gupta A, Shaw A, Roberts I, Mundel P, et al. Inhibitory smads and tgf-Beta signaling in glomerular cells. J Am Soc Nephrol. 2002;13:2657-66 pubmed
    Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-beta, receptor tyrosine kinase (RTK), JAK/STAT, and NF-kappaB pathways...
  17. Li Q. Inhibitory SMADs: potential regulators of ovarian function. Biol Reprod. 2015;92:50 pubmed publisher
    ..Emerging evidence supports that inhibitory SMADs are potential regulators of ovarian function. Further efforts and new genetic models are needed to unveil the role of inhibitory SMADs in the ovary. ..
  18. 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
    ..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 alveolar stages of ..
  19. Nishimura Y, Kurisaki A, Nakanishi M, Ohnuma K, Ninomiya N, Komazaki S, et al. Inhibitory Smad proteins promote the differentiation of mouse embryonic stem cells into ependymal-like ciliated cells. Biochem Biophys Res Commun. 2010;401:1-6 pubmed publisher
    ..In this study, we found that inhibitory Smad proteins, Smad7 and Smad6, significantly promoted the differentiation of mouse embryonic stem (ES) cells into ciliated cells...
  20. Schwalm S, Beyer S, Frey H, Haceni R, Grammatikos G, Thomas D, et al. Sphingosine Kinase-2 Deficiency Ameliorates Kidney Fibrosis by Up-Regulating Smad7 in a Mouse Model of Unilateral Ureteral Obstruction. Am J Pathol. 2017;187:2413-2429 pubmed publisher
    ..More important, these changes were associated with increased expression of the antifibrotic protein Smad7 and higher levels of sphingosine in Sphk2-/- UUO kidneys...
  21. Saika S, Ikeda K, Yamanaka O, Miyamoto T, Ohnishi Y, Sato M, et al. Expression of Smad7 in mouse eyes accelerates healing of corneal tissue after exposure to alkali. Am J Pathol. 2005;166:1405-18 pubmed
    ..in a corneal alkali burn model using mice treated topically with an adenovirus (Ad) expressing inhibitory Smad7 and mice with a targeted deletion of the TGF-beta/activin signaling mediator Smad3...
  22. Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett A, et al. Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J Clin Invest. 2009;119:3301-10 pubmed publisher
    ..We could not rescue PAA morphogenesis by restoring neural crest Chd7 expression. Rather, biallelic expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal PAA development...
  23. Han G, Li F, Ten Dijke P, Wang X. Temporal smad7 transgene induction in mouse epidermis accelerates skin wound healing. Am J Pathol. 2011;179:1768-79 pubmed publisher
    The expression of Smad7, a tumor growth factor-β (TGFβ) antagonist, is increased during cutaneous wound healing...
  24. Taniguchi K, Anderson A, Melhuish T, Carlton A, Manukyan A, Sutherland A, et al. Genetic and Molecular Analyses indicate independent effects of TGIFs on Nodal and Gli3 in neural tube patterning. Eur J Hum Genet. 2017;25:208-215 pubmed publisher
    ..Based on this work, we propose a model for distinct functions of Tgifs in the Nodal and Shh/Gli3 pathways during forebrain development...
  25. Zhao Y, Thornton A, Kinney M, Ma C, Spinner J, Fuss I, et al. The deubiquitinase CYLD targets Smad7 protein to regulate transforming growth factor β (TGF-β) signaling and the development of regulatory T cells. J Biol Chem. 2011;286:40520-30 pubmed publisher
    ..Under endogenous conditions, CYLD formed a complex with Smad7 that facilitated CYLD deubiquitination of Smad7 at lysine 360 and 374 residues...
  26. Vujic Spasic M, Sparla R, Mleczko Sanecka K, Migas M, Breitkopf Heinlein K, Dooley S, et al. Smad6 and Smad7 are co-regulated with hepcidin in mouse models of iron overload. Biochim Biophys Acta. 2013;1832:76-84 pubmed publisher
    The inhibitory Smad7 acts as a critical suppressor of hepcidin, the major regulator of systemic iron homeostasis...
  27. Nakao A, Miike S, Hatano M, Okumura K, Tokuhisa T, Ra C, et al. Blockade of transforming growth factor beta/Smad signaling in T cells by overexpression of Smad7 enhances antigen-induced airway inflammation and airway reactivity. J Exp Med. 2000;192:151-8 pubmed
    ..To address this issue, we developed transgenic mice expressing Smad7, an intracellular antagonist of TGF-beta/Smad signaling, selectively in mature T cells using a plasmid construct ..
  28. Arsura M, Panta G, Bilyeu J, Cavin L, Sovak M, Oliver A, et al. Transient activation of NF-kappaB through a TAK1/IKK kinase pathway by TGF-beta1 inhibits AP-1/SMAD signaling and apoptosis: implications in liver tumor formation. Oncogene. 2003;22:412-25 pubmed
    ..Furthermore, TGF-beta1-mediated upregulation of Smad7 appeared independent of NF-kappaB...
  29. Benchabane H, Wrana J. GATA- and Smad1-dependent enhancers in the Smad7 gene differentially interpret bone morphogenetic protein concentrations. Mol Cell Biol. 2003;23:6646-61 pubmed
    b>Smad7, an inhibitor of transforming growth factor beta superfamily signaling, is induced by bone morphogenetic protein (BMP) in an inhibitory feedback loop...
  30. Kleiter I, Song J, Lukas D, Hasan M, Neumann B, Croxford A, et al. Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain. 2010;133:1067-81 pubmed publisher
    ..and used mice with conditional deletion or over-expression of the transforming growth factor-beta inhibitor Smad7, to delineate the role of Smad7 in T cell differentiation and autoimmune neuroinflammation...
  31. Marschallinger J, Krampert M, Couillard Despres S, Heuchel R, Bogdahn U, Aigner L. Age-dependent and differential effects of Smad7ΔEx1 on neural progenitor cell proliferation and on neurogenesis. Exp Gerontol. 2014;57:149-54 pubmed publisher
    We recently reported that young (3 to 4months old) mice lacking Exon 1 of the Smad7 gene (S7ΔEx1 mice) show enhanced proliferation of neural stem and progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) and in the ..
  32. Ka S, Yeh Y, Huang X, Chao T, Hung Y, Yu C, et al. Kidney-targeting Smad7 gene transfer inhibits renal TGF-β/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice. Diabetologia. 2012;55:509-19 pubmed publisher
    ..We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes...
  33. Kitamura K, Aota S, Sakamoto R, Yoshikawa S, Okazaki K. Smad7 selectively interferes with different pathways of activin signaling and inhibits erythroid leukemia cell differentiation. Blood. 2000;95:3371-9 pubmed
    ..A distant family member, Smad7, is expressed in most mammalian tissues and cells and prevents TGF-beta signaling...
  34. Ellsworth B, Burns A, Escudero K, Duval D, Nelson S, Clay C. The gonadotropin releasing hormone (GnRH) receptor activating sequence (GRAS) is a composite regulatory element that interacts with multiple classes of transcription factors including Smads, AP-1 and a forkhead DNA binding protein. Mol Cell Endocrinol. 2003;206:93-111 pubmed
    ..We suggest that GRAS is a composite regulatory element whose functional activity is dependent on the organization of a multi-protein complex consisting of Smads, AP-1 and a member of the forkhead family of DNA binding proteins. ..
  35. Tang Y, Liu Z, Zhao L, Clemens T, Cao X. Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion. J Biol Chem. 2008;283:23956-63 pubmed publisher
    ..Here we show that Smad7 promotes cell-cell adhesion by stabilizing beta-catenin and consequently increases the beta-catenin-E-cadherin ..
  36. Hollis Moffatt J, Hook S, Merriman T. Colocalization of mouse autoimmune diabetes loci Idd21.1 and Idd21.2 with IDDM6 (human) and Iddm3 (rat). Diabetes. 2005;54:2820-5 pubmed
    ..1-21.2 in mouse. Further genetic localization of Idd21.1 and Idd21.2 could expedite characterization of the human IDDM6 region. ..
  37. Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isshiki K, et al. SIRT1 inhibits transforming growth factor beta-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation. J Biol Chem. 2007;282:151-8 pubmed
    ..In this study, we have examined the likelihood and role of the interaction between SIRT1 and Smad7, which mediates transforming growth factor beta (TGFbeta)-induced apoptosis in renal glomerular mesangial cells...
  38. Nagarajan R, Zhang J, Li W, Chen Y. Regulation of Smad7 promoter by direct association with Smad3 and Smad4. J Biol Chem. 1999;274:33412-8 pubmed
    b>Smad7 is a regulatory Smad protein that is able to antagonize signal transduction by transforming growth factor-beta (TGF-beta) and activin receptors...
  39. Valdimarsdottir G, Goumans M, Itoh F, Itoh S, Heldin C, Ten Dijke P. Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cells. BMC Cell Biol. 2006;7:16 pubmed
    ..b>Smad7 and protein phosphatase 1alpha (PP1alpha) mRNA expression levels were found to be specifically upregulated by TGF-..
  40. Lai H, Klisch T, Roberts R, Zoghbi H, Johnson J. In vivo neuronal subtype-specific targets of Atoh1 (Math1) in dorsal spinal cord. J Neurosci. 2011;31:10859-71 pubmed publisher
    ..These targets, Klf7, Rab15, Rassf4, Selm, and Smad7, have diverse functions that range from transcription factors to regulators of endocytosis and signaling pathways...
  41. Zhu L, Wang L, Wang X, Luo X, Yang L, Zhang R, et al. Hepatic deletion of Smad7 in mouse leads to spontaneous liver dysfunction and aggravates alcoholic liver injury. PLoS ONE. 2011;6:e17415 pubmed publisher
    ..b>Smad7 is an intracellular negative regulator of TGF-β signaling...
  42. Islam S, Mokhtari R, Kumar S, Maalouf J, Arab S, Yeger H, et al. Spatio-temporal distribution of Smads and role of Smads/TGF-β/BMP-4 in the regulation of mouse bladder organogenesis. PLoS ONE. 2013;8:e61340 pubmed publisher
    ..Smad6 and Smad7 showed overlapping expression with R-Smads, which are critical for bladder development. In bladder explants (E12...
  43. Tang S, Snider P, Firulli A, Conway S. Trigenic neural crest-restricted Smad7 over-expression results in congenital craniofacial and cardiovascular defects. Dev Biol. 2010;344:233-47 pubmed publisher
    b>Smad7 is a negative regulator of TGFbeta superfamily signaling. Using a three-component triple transgenic system, expression of the inhibitory Smad7 was induced via doxycycline within the NCC lineages at pre- and post-migratory stages...
  44. 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
    Inhibitory Smad, Smad7, is a potent inhibitor of TGF-beta (transforming growth factor-beta) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads)...