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. Kleiter I, Pedre X, Mueller A, Poeschl P, Couillard Despres S, Spruss T, et al. Inhibition of Smad7, a negative regulator of TGF-beta signaling, suppresses autoimmune encephalomyelitis. J Neuroimmunol. 2007;187:61-73 pubmed
    We studied the role of the Transforming growth factor (TGF)-beta signaling antagonist Smad7 in autoimmune central nervous system (CNS) inflammation by using specific antisense oligonucleotides (Smad7-as)...
  2. 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...
  3. 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 ..
  4. Hamzavi J, Ehnert S, Godoy P, Ciuclan L, Weng H, Mertens P, et al. Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice. J Cell Mol Med. 2008;12:2130-44 pubmed publisher
    ..Smad-dependent TGF-beta effects are blunted by antagonistic Smad7, which is transcriptionally activated as an immediate early response upon initiation of TGF-beta signalling in ..
  5. 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
    ..as a downstream mediator of transforming growth factor-? (TGF-?) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear...
  6. 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 ..
  7. 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...
  8. 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...
  9. 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 ..
  10. Blank U, Karlsson G, Moody J, Utsugisawa T, Magnusson M, Singbrant S, et al. Smad7 promotes self-renewal of hematopoietic stem cells. Blood. 2006;108:4246-54 pubmed
    ..of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs...

Detail Information

Publications92

  1. Kleiter I, Pedre X, Mueller A, Poeschl P, Couillard Despres S, Spruss T, et al. Inhibition of Smad7, a negative regulator of TGF-beta signaling, suppresses autoimmune encephalomyelitis. J Neuroimmunol. 2007;187:61-73 pubmed
    We studied the role of the Transforming growth factor (TGF)-beta signaling antagonist Smad7 in autoimmune central nervous system (CNS) inflammation by using specific antisense oligonucleotides (Smad7-as)...
  2. 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...
  3. 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 ..
  4. Hamzavi J, Ehnert S, Godoy P, Ciuclan L, Weng H, Mertens P, et al. Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice. J Cell Mol Med. 2008;12:2130-44 pubmed publisher
    ..Smad-dependent TGF-beta effects are blunted by antagonistic Smad7, which is transcriptionally activated as an immediate early response upon initiation of TGF-beta signalling in ..
  5. 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
    ..as a downstream mediator of transforming growth factor-? (TGF-?) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear...
  6. 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 ..
  7. 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...
  8. 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...
  9. 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 ..
  10. Blank U, Karlsson G, Moody J, Utsugisawa T, Magnusson M, Singbrant S, et al. Smad7 promotes self-renewal of hematopoietic stem cells. Blood. 2006;108:4246-54 pubmed
    ..of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs...
  11. He W, Li A, Wang D, Han S, Zheng B, Goumans M, et al. Overexpression of Smad7 results in severe pathological alterations in multiple epithelial tissues. EMBO J. 2002;21:2580-90 pubmed
    Biochemical studies have shown that Smad7 blocks signal transduction of transforming growth factor beta (TGFbeta); however, its in vivo functions are largely unknown...
  12. Li R, Rosendahl A, Brodin G, Cheng A, Ahgren A, Sundquist C, et al. Deletion of exon I of SMAD7 in mice results in altered B cell responses. J Immunol. 2006;176:6777-84 pubmed
    ..b>Smad7 is induced by the TGF-beta superfamily members and negatively modulates their signaling, thus acting in a negative,..
  13. Liu X, Lee J, Cooley M, Bhogte E, Hartley S, Glick A. Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion in a mouse model for squamous cell carcinoma. Cancer Res. 2003;63:7760-8 pubmed
    b>Smad7 and Smad6 are inhibitory Smads that block transforming growth factor-beta (TGF-beta) superfamily signal transduction...
  14. 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. ..
  15. Pulaski L, Landstrom M, Heldin C, Souchelnytskyi S. Phosphorylation of Smad7 at Ser-249 does not interfere with its inhibitory role in transforming growth factor-beta-dependent signaling but affects Smad7-dependent transcriptional activation. J Biol Chem. 2001;276:14344-9 pubmed
    ..b>Smad7 was identified as a potent inhibitor of TGF-beta-dependent signaling...
  16. Gruber T, Hinterleitner R, Hermann Kleiter N, Meisel M, Kleiter I, Wang C, et al. Cbl-b mediates TGF? 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 TGF? receptor (TGF?R) signaling, is a key downstream effector target of Cbl-..
  17. Lan H, Mu W, Tomita N, Huang X, Li J, Zhu H, et al. Inhibition of renal fibrosis by gene transfer of inducible Smad7 using ultrasound-microbubble system in rat UUO model. J Am Soc Nephrol. 2003;14:1535-48 pubmed
    ..and renal fibrosis in a rat unilateral ureteral obstruction (UUO) model by transferring a doxycycline-regulated Smad7 gene or control empty vectors using an ultrasound-microbubble (Optison)-mediated system...
  18. 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)...
  19. 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.
  20. 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...
  21. Krampert M, Chirasani S, Wachs F, Aigner R, Bogdahn U, Yingling J, et al. Smad7 regulates the adult neural stem/progenitor cell pool in a transforming growth factor beta- and bone morphogenetic protein-independent manner. Mol Cell Biol. 2010;30:3685-94 pubmed publisher
    ..Here, we investigated neurogenesis in a hypomorphic mouse model for the TGF-beta and BMP inhibitor Smad7, with the hypothesis that NPC proliferation might be reduced due to increased TGF-beta and BMP signaling...
  22. Wang W, Huang X, Li A, Liu F, Li J, Truong L, et al. Signaling mechanism of TGF-beta1 in prevention of renal inflammation: role of Smad7. J Am Soc Nephrol. 2005;16:1371-83 pubmed
    ..of renal inflammation in TGF-beta1 transgenic mice was also associated with a marked upregulation of renal Smad7 and IkappaBalpha and a suppression of NF-kappaB activation in the diseased kidney (all P < 0.01)...
  23. 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...
  24. Song Q, Zhong L, Chen C, Tang Z, Liu H, Zhou Y, et al. miR-21 synergizes with BMP9 in osteogenic differentiation by activating the BMP9/Smad signaling pathway in murine multilineage cells. Int J Mol Med. 2015;36:1497-506 pubmed publisher
    ..Furthermore, miR-21 was confirmed to promote the osteogenic differentiation of the MMCs by suppressing Smad7, which negatively regulates the osteogenic differentiation of MMCs...
  25. Miyake T, Alli N, McDermott J. Nuclear function of Smad7 promotes myogenesis. Mol Cell Biol. 2010;30:722-35 pubmed publisher
    In the "canonical" view of transforming growth factor beta (TGF-beta) signaling, Smad7 plays an inhibitory role...
  26. Denissova N, Pouponnot C, Long J, He D, Liu F. Transforming growth factor beta -inducible independent binding of SMAD to the Smad7 promoter. Proc Natl Acad Sci U S A. 2000;97:6397-402 pubmed
    ..In an effort to search for TGF-beta-inducible genes, we used a subtractive screening method and identified human Smad7, which can antagonize TGF-beta signaling and is rapidly up-regulated by TGF-beta...
  27. Kitamura K, Aota S, Sakamoto R, Emori T, Okazaki K. Smad7 induces G0/G1 cell cycle arrest in mesenchymal cells by inhibiting the expression of G1 cyclins. Dev Growth Differ. 2005;47:537-52 pubmed
    ..In this study, we examined the effects of sustained Smad7 expression in cultured cells...
  28. Kuang C, Xiao Y, Liu X, Stringfield T, Zhang S, Wang Z, et al. In vivo disruption of TGF-beta signaling by Smad7 leads to premalignant ductal lesions in the pancreas. Proc Natl Acad Sci U S A. 2006;103:1858-63 pubmed
    ..the development of pancreatic cancers, we generated a transgenic mouse model with pancreas-specific expression of Smad7, a specific inhibitor of TGF-beta signaling...
  29. Souilhol C, Gonneau C, Lendínez J, Batsivari A, Rybtsov S, Wilson H, et al. Inductive interactions mediated by interplay of asymmetric signalling underlie development of adult haematopoietic stem cells. Nat Commun. 2016;7:10784 pubmed publisher
  30. Lee D, Lee D, Zhou L, Zhou L, Zhou Z, Xie J, et al. Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis. Blood. 2010;115:3136-45 pubmed publisher
    ..These results reveal a novel mechanism underlying neogenin regulation of HJV-BMP signaling...
  31. Jing L, Zhou L, Zhang F, Li W, Sang Y. Tenascin-x facilitates myocardial fibrosis and cardiac remodeling through transforming growth factor-?1 and peroxisome proliferator-activated receptor ? in alcoholic cardiomyopathy. Chin Med J (Engl). 2011;124:390-5 pubmed
    ..001). Tenascin-x is an initiator of myocardial fibrosis and ACM development via upregulation of TGF?(1) and downregulation of PPAR?. ..
  32. Shukla A, Yang Y, Madanikia S, Ho Y, Li M, Sanchez V, et al. Elevating CLIC4 in Multiple Cell Types Reveals a TGF- Dependent Induction of a Dominant Negative Smad7 Splice Variant. PLoS ONE. 2016;11:e0161410 pubmed publisher
    ..The alternatively spliced Smad7? variant is missing 94bp in exon 4 of Smad 7 and is conserved between mouse and human cells...
  33. Ishida Y, Kondo T, Takayasu T, Iwakura Y, Mukaida N. The essential involvement of cross-talk between IFN-gamma and TGF-beta in the skin wound-healing process. J Immunol. 2004;172:1848-55 pubmed
    ..evidenced by increases in the levels of total and phosphorylated Smad2 and a reciprocal decrease in the levels of Smad7. These results demonstrate that there is crosstalk between the IFN-gamma/Stat1 and TGF-beta1/Smad signaling ..
  34. Iwai T, Murai J, Yoshikawa H, Tsumaki N. Smad7 Inhibits chondrocyte differentiation at multiple steps during endochondral bone formation and down-regulates p38 MAPK pathways. J Biol Chem. 2008;283:27154-64 pubmed publisher
    ..In vitro studies have demonstrated that Smad7 regulates transforming growth factor-beta and BMP signals by inhibiting Smad pathways in chondrocytes...
  35. Kelly C, Thymiakou E, Dixon J, Tanaka S, Godwin J, Episkopou V. Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon extension. PLoS Biol. 2013;11:e1001538 pubmed publisher
    ..Together the above data reveal an involvement of BMP-Smad signaling in motor axon advancement. ..
  36. 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...
  37. Mleczko Sanecka K, Casanovas G, Ragab A, Breitkopf K, Muller A, Boutros M, et al. SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression. Blood. 2010;115:2657-65 pubmed publisher
    ..By using high-throughput siRNA screening we identified SMAD7 as a potent hepcidin suppressor...
  38. Mahoney J, Mori M, Szymaniak A, Varelas X, Cardoso W. The hippo pathway effector Yap controls patterning and differentiation of airway epithelial progenitors. Dev Cell. 2014;30:137-50 pubmed publisher
    ..Our data reveal a role for the Hippo-Yap pathway in integrating growth-factor-induced cues in the developing and adult lung potentially key for homeostasis and regeneration repair. ..
  39. Zhang X, Zhang J, Bauer A, Zhang L, Selinger D, Lu C, et al. Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. EMBO J. 2013;32:996-1007 pubmed publisher
    ..Moreover, UBE2O and SMAD6 cooperated in the regulation of BMP7-induced adipogenesis. ..
  40. Zhu Z, Xu Y, Zhao J, Liu Q, Feng W, Fan J, et al. miR-367 promotes epithelial-to-mesenchymal transition and invasion of pancreatic ductal adenocarcinoma cells by targeting the Smad7-TGF-β signalling pathway. Br J Cancer. 2015;112:1367-75 pubmed publisher
    Aberrant Smad7 expression contributes to the invasion and metastasis of pancreatic cancer cells...
  41. He J, Sun X, Qian K, Liu X, Wang Z, Chen Y. Protection of cerulein-induced pancreatic fibrosis by pancreas-specific expression of Smad7. Biochim Biophys Acta. 2009;1792:56-60 pubmed publisher
    ..We analyzed the in vivo role of TGF-beta pathway in pancreatic fibrosis in this study. Smad7, an intracellular inhibitory protein that antagonizes TGF-beta signaling, was specifically expressed in the ..
  42. Itman C, Loveland K. SMAD expression in the testis: an insight into BMP regulation of spermatogenesis. Dev Dyn. 2008;237:97-111 pubmed
    ..Smad1, Smad5, Smad8, Smad4, Smad6, and Smad7 expression is ubiquitous during testis development but becomes cell-specific in the adult...
  43. Weng H, Ciuclan L, Liu Y, Hamzavi J, Godoy P, Gaitantzi H, et al. Profibrogenic transforming growth factor-beta/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes. Hepatology. 2007;46:1257-70 pubmed
    ..CTGF expression in the liver tissue of TGF-beta transgenic mice correlated with serum TGF-beta levels. Smad7 overexpression in cultured hepatocytes abrogated TGF-beta-dependent and intrinsic CTGF expression, indicating that ..
  44. Shum E, Jones S, Shao A, Dumdie J, Krause M, Chan W, et al. The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay. Cell. 2016;165:382-95 pubmed publisher
    ..Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events. ..
  45. Rizzo A, Waldner M, Stolfi C, Sarra M, Fina D, Becker C, et al. Smad7 expression in T cells prevents colitis-associated cancer. Cancer Res. 2011;71:7423-32 pubmed publisher
    ..In this study, we investigated the role of the TGF? signaling inhibitor Smad7 in CAC pathogenesis...
  46. Weng Q, Chen Y, Wang H, Xu X, Yang B, He Q, et al. Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system. Neuron. 2012;73:713-28 pubmed publisher
    ..Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss...
  47. Cohen T, Kollias H, Liu N, Ward C, Wagner K. Genetic disruption of Smad7 impairs skeletal muscle growth and regeneration. J Physiol. 2015;593:2479-97 pubmed publisher
    b>Smad7 is an intracellular antagonist of transforming growth factor-β signalling pathways and modulates muscle growth in vivo...
  48. Halder S, Rachakonda G, Deane N, Datta P. Smad7 induces hepatic metastasis in colorectal cancer. Br J Cancer. 2008;99:957-65 pubmed publisher
    ..We previously reported that overexpression of Smad7 in colon adenocarcinoma (FET) cells induces tumorigenicity by blocking TGF-beta-induced growth inhibition and ..
  49. Warner D, Pisano M, Roberts E, Greene R. Identification of three novel Smad binding proteins involved in cell polarity. FEBS Lett. 2003;539:167-73 pubmed
  50. Warner D, Horn K, Mudd L, Webb C, Greene R, Pisano M. PRDM16/MEL1: a novel Smad binding protein expressed in murine embryonic orofacial tissue. Biochim Biophys Acta. 2007;1773:814-20 pubmed
    ..Taken together, these results demonstrate that PRDM16/MEL1 is a Smad binding protein that may be important for development of orofacial structures through modulation of the TGFbeta signaling pathway. ..
  51. Blaney Davidson E, Vitters E, van den Berg W, van der Kraan P. TGF beta-induced cartilage repair is maintained but fibrosis is blocked in the presence of Smad7. Arthritis Res Ther. 2006;8:R65 pubmed
    ..repair and whether TGFbeta-induced fibrosis was blocked by local expression of the intracellular TGFbeta inhibitor Smad7. We inflicted cartilage damage by injection of interleukin-1 (IL-1) into murine knee joints...
  52. 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...
  53. Liu G, Li Y, Huang X, Wei L, Chen H, Shi Y, et al. Disruption of Smad7 promotes ANG II-mediated renal inflammation and fibrosis via Sp1-TGF-?/Smad3-NF.?B-dependent mechanisms in mice. PLoS ONE. 2013;8:e53573 pubmed publisher
    b>Smad7 is an inhibitory Smad and plays a protective role in obstructive and diabetic kidney disease. However, the role and mechanisms of Smad7 in hypertensive nephropathy remains unexplored...
  54. 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...
  55. 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. ..
  56. 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. ..
  57. Lei X, Fu W, Kim Kaneyama J, Omoto T, Miyazaki T, Li B, et al. Hic-5 deficiency attenuates the activation of hepatic stellate cells and liver fibrosis through upregulation of Smad7 in mice. J Hepatol. 2016;64:110-7 pubmed publisher
    ..the absence of Hic-5 significantly inhibited the TGF-β/Smad2 signaling pathway, proved by increasing Smad7 expression, resulting in reduced collagen production and α-smooth muscle actin expression in the activated HSCs...
  58. 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 ..
  59. 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...
  60. Ha Thi H, Kim H, Choi S, Kang J, Kim S, Hong S. Smad7 Modulates Epidermal Growth Factor Receptor Turnover through Sequestration of c-Cbl. Mol Cell Biol. 2015;35:2841-50 pubmed publisher
    ..For the maintenance of homeostasis, EGF signaling should be tightly regulated to prevent the aberrant activation. Smad7 has been known as inhibitory Smad that blocks the signal transduction of transforming growth factor β...
  61. Fu S, Tang Y, Huang X, Feng M, Xu A, Lan H. Smad7 protects against acute kidney injury by rescuing tubular epithelial cells from the G1 cell cycle arrest. Clin Sci (Lond). 2017;131:1955-1969 pubmed publisher
    b>Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored...
  62. 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...
  63. 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...
  64. 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...
  65. 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-? (TGF?) antagonist, is increased during cutaneous wound healing...
  66. 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 ? (TGF-?) 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...
  67. 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...
  68. 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. ..
  69. 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...
  70. 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...
  71. 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 ..
  72. 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...
  73. Marschallinger J, Krampert M, Couillard Despres S, Heuchel R, Bogdahn U, Aigner L. Age-dependent and differential effects of Smad7?Ex1 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 (S7?Ex1 mice) show enhanced proliferation of neural stem and progenitor cells (NPCs) in the hippocampal dentate gyrus (DG) and in the subventricular ..
  74. Ka S, Yeh Y, Huang X, Chao T, Hung Y, Yu C, et al. Kidney-targeting Smad7 gene transfer inhibits renal TGF-?/MAD homologue (SMAD) and nuclear factor ?B (NF-?B) 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...
  75. 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...
  76. Braunger B, Pielmeier S, Demmer C, Landstorfer V, Kawall D, Abramov N, et al. TGF-? signaling protects retinal neurons from programmed cell death during the development of the mammalian eye. J Neurosci. 2013;33:14246-58 pubmed publisher
    ..cell death in the mouse retina by direct and specific molecular targeting of TGF-? type II receptor (T?RII) and Smad7 in retinal progenitor cells...
  77. Xiao L, Peng X, Liu F, Tang C, Hu C, Xu X, et al. AKT regulation of mesothelial-to-mesenchymal transition in peritoneal dialysis is modulated by Smurf2 and deubiquitinating enzyme USP4. BMC Cell Biol. 2015;16:7 pubmed publisher
    ..regulatory factor 2 (Smurf2), Vimentin and fibronectin (FN), and decreased expression of mothers against decapentaplegic homolog 7 (Smad7) and Zonula Occludens protein 1(ZO-1) in mice undergoing PD treatment and in TGF-β1 ..
  78. Snider P, Tang S, Lin G, Wang J, Conway S. Generation of Smad7(-Cre) recombinase mice: A useful tool for the study of epithelial-mesenchymal transformation within the embryonic heart. Genesis. 2009;47:469-75 pubmed publisher
    b>Smad7 can be induced by various transforming growth factor-beta superfamily ligands and negatively modulates their signaling, thus acting in a negative, autocrine feedback manner...
  79. 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 ..
  80. 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. ..
  81. 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. ..
  82. 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...
  83. Dattaroy D, Pourhoseini S, Das S, Alhasson F, Seth R, Nagarkatti M, et al. Micro-RNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2015;308:G298-312 pubmed publisher
    ..the nucleus, increased immunoreactivity against Col1?, and ?-SMA with a concomitant decrease in protein levels of SMAD7. Mice that were deficient in leptin or p47phox had decreased activated NF-?B and miR21 levels, suggesting the role ..
  84. 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-..
  85. 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...
  86. 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...
  87. 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-? signaling...
  88. Islam S, Mokhtari R, Kumar S, Maalouf J, Arab S, Yeger H, et al. Spatio-temporal distribution of Smads and role of Smads/TGF-?/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...
  89. 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...
  90. 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)...