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Gene Review

Smad7  -  SMAD family member 7

Rattus norvegicus

Synonyms: MAD homolog 7, Madh7, Mothers against DPP homolog 7, Mothers against decapentaplegic homolog 7, SMAD 7
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Disease relevance of Smad7


High impact information on Smad7

  • Such a beneficial effect was also observed when Smad7 was expressed in animals with established fibrosis [7].
  • Animals received injections of an adenovirus carrying Smad7 cDNA into the portal vein during surgery and via the tail vein at later stages [7].
  • Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats [7].
  • RESULTS: Smad7-overexpressing BDL rats displayed reduced collagen and alpha-SMA expression and reduced hydroxyproline content in the liver, when compared with animals administered AdLacZ [7].
  • Smad7 did not decrease expression of alpha-SMA, but immunofluorescent staining with anti alpha-SMA antibodies displayed destruction of the fibrillar organization of the actin cytoskeleton [7].

Chemical compound and disease context of Smad7

  • To investigate a negative regulatory role of Smad7 in renal fibrosis, the Smad 7 gene was stably transfected and its expression was tightly controlled by doxycycline into NRK52E cells [8].
  • RESULTS: Compared with the hepatic fibrosis models, the levels of TGF-beta1, TRII mRNA and the expression Smad3 significantly decreased in the two treated groups, and the expression of Smad7 was significantly increased in the liver of rats treated with perindopril or valsartan (P < 0.05 or P < 0.01) [9].

Biological context of Smad7


Anatomical context of Smad7


Associations of Smad7 with chemical compounds

  • Groups of six rats were subjected to 5/6 nephrectomy and received renal arterial injection of a doxycycline-regulated Smad7 gene or control empty vector using an ultrasound-microbubble-mediated system [2].
  • Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression [15].
  • Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway [15].
  • Smad7 is induced by norepinephrine and protects rat hepatocytes from activin A-induced growth inhibition [3].
  • This initiation of transcription is dependent on functional tyrosine kinase receptors and can be blocked by Smad7 [16].

Enzymatic interactions of Smad7

  • The different regulation of inhibitory Smad-7 was detected in irradiated and irradiated plus anti-TGFbeta1 treated animals by semiquantitative RT-PCR and the nucleocytoplasmic shuttling of phosphorylated Smad-3 was shown by isolation of nuclear proteins and Western blot analysis [17].

Regulatory relationships of Smad7

  • Conversely, Id1 overexpression in HSCs enhanced cell activation and circumvented Smad7-dependent inhibition of transdifferentiation [1].
  • Interestingly, Smad6 and Smad7 expression was also up-regulated in cells with increased Smad2 activation [18].
  • Smad6 and Smad7 inhibit signaling by members of the TGF-beta superfamily [14].
  • Furthermore, we report that the overexpression of Smad 7 mRNA could induce an activation of c-Jun N-terminal kinase, because of the observed c-Jun overexpression, activation, and nuclear translocation leading to an increase in the transcription of the proapoptotic factor Fas-L [19].
  • These results indicated that ERK activation negatively regulated Smad7 transcription possibly by inhibiting translocation of Smad complex to nuclei [20].

Other interactions of Smad7

  • Overexpression of the TGF-beta antagonist Smad7 inhibits transdifferentiation and arrests HSCs in a quiescent stage [1].
  • Ectopic Smad7 expression in HSCs strongly reduced Id1 mRNA and protein expression [1].
  • IFN-gamma treatment of MEC activates and relocalizes signal transducer and activator of transcription-1 (STAT-1) to induce an inhibitor SMAD, SMAD7 [21].
  • The mechanisms might be associated with their effects of down-regulating TGF-beta1, TRII mRNA and Smad3, and up-regulating Smad7 [22].
  • We investigated expressions and localizations of TGR1, Smad2, Smad4, and Smad7 by using semi-quantitative RT-PCR and immunohistochemistry in preneoplastic lesions during rat chemical hepatocarcinogenesis induced by Solt and Farber's method [23].

Analytical, diagnostic and therapeutic context of Smad7


  1. Id1 is a critical mediator in TGF-beta-induced transdifferentiation of rat hepatic stellate cells. Wiercinska, E., Wickert, L., Denecke, B., Said, H.M., Hamzavi, J., Gressner, A.M., Thorikay, M., ten Dijke, P., Mertens, P.R., Breitkopf, K., Dooley, S. Hepatology (2006) [Pubmed]
  2. Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks transforming growth factor-beta signaling and fibrosis in rat remnant kidney. Hou, C.C., Wang, W., Huang, X.R., Fu, P., Chen, T.H., Sheikh-Hamad, D., Lan, H.Y. Am. J. Pathol. (2005) [Pubmed]
  3. Smad7 is induced by norepinephrine and protects rat hepatocytes from activin A-induced growth inhibition. Kanamaru, C., Yasuda, H., Takeda, M., Ueda, N., Suzuki, J., Tsuchida, T., Mashima, H., Ohnishi, H., Fujita, T. J. Biol. Chem. (2001) [Pubmed]
  4. Localization of Smad6 and Smad7 in the rat kidney and their regulated expression in the anti-Thy-1 nephritis. Uchida, K., Nitta, K., Kobayashi, H., Kawachi, H., Shimizu, F., Yumura, W., Nihei, H. Mol. Cell Biol. Res. Commun. (2000) [Pubmed]
  5. Blockade of NFkappaB activation and renal inflammation by ultrasound-mediated gene transfer of Smad7 in rat remnant kidney. Ng, Y.Y., Hou, C.C., Wang, W., Huang, X.R., Lan, H.Y. Kidney Int. Suppl. (2005) [Pubmed]
  6. Smad7 transgene attenuates peritoneal fibrosis in uremic rats treated with peritoneal dialysis. Guo, H., Leung, J.C., Lam, M.F., Chan, L.Y., Tsang, A.W., Lan, H.Y., Lai, K.N. J. Am. Soc. Nephrol. (2007) [Pubmed]
  7. Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats. Dooley, S., Hamzavi, J., Breitkopf, K., Wiercinska, E., Said, H.M., Lorenzen, J., Ten Dijke, P., Gressner, A.M. Gastroenterology (2003) [Pubmed]
  8. Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation. Li, J.H., Zhu, H.J., Huang, X.R., Lai, K.N., Johnson, R.J., Lan, H.Y. J. Am. Soc. Nephrol. (2002) [Pubmed]
  9. Effects of perindopril and valsartan on expression of transforming growth factor-beta-Smads in experimental hepatic fibrosis in rats. Xu, W., Song, S., Huang, Y., Gong, Z. J. Gastroenterol. Hepatol. (2006) [Pubmed]
  10. Smad7 mediates transforming growth factor-beta-induced apoptosis in mesangial cells. Okado, T., Terada, Y., Tanaka, H., Inoshita, S., Nakao, A., Sasaki, S. Kidney Int. (2002) [Pubmed]
  11. Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart. Wang, B., Hao, J., Jones, S.C., Yee, M.S., Roth, J.C., Dixon, I.M. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  12. Genomic locus and promoter region of rat Smad7, an important antagonist of TGFbeta signaling. Stopa, M., Benes, V., Ansorge, W., Gressner, A.M., Dooley, S. Mamm. Genome (2000) [Pubmed]
  13. Ectopic expression of Smad7 inhibits transforming growth factor-beta responses in vascular smooth muscle cells. Kato, S., Ueda, S., Tamaki, K., Fujii, M., Miyazono, K., ten Dijke, P., Morimatsu, M., Okuda, S. Life Sci. (2001) [Pubmed]
  14. Localization of Smads, the TGF-beta family intracellular signaling components during endochondral ossification. Sakou, T., Onishi, T., Yamamoto, T., Nagamine, T., Sampath, T., Ten Dijke, P. J. Bone Miner. Res. (1999) [Pubmed]
  15. Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway. Hama, K., Ohnishi, H., Aoki, H., Kita, H., Yamamoto, H., Osawa, H., Sato, K., Tamada, K., Mashima, H., Yasuda, H., Sugano, K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  16. Nerve growth factor mediates activation of the Smad pathway in PC12 cells. Lutz, M., Krieglstein, K., Schmitt, S., ten Dijke, P., Sebald, W., Wizenmann, A., Knaus, P. Eur. J. Biochem. (2004) [Pubmed]
  17. Smad-3 and Smad-7 expression following anti-transforming growth factor beta 1 (TGFbeta1)-treatment in irradiated rat tissue. Schultze-Mosgau, S., Blaese, M.A., Grabenbauer, G., Wehrhan, F., Kopp, J., Amann, K., Rodemann, H.P., Rödel, F. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. (2004) [Pubmed]
  18. Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration. Brodin, G., ten Dijke, P., Funa, K., Heldin, C.H., Landström, M. Cancer Res. (1999) [Pubmed]
  19. Alteration of transforming growth factor-beta signaling system expression in adult rat germ cells with a chronic apoptotic cell death process after fetal androgen disruption. Maire, M., Florin, A., Kaszas, K., Regnier, D., Contard, P., Tabone, E., Mauduit, C., Bars, R., Benahmed, M. Endocrinology (2005) [Pubmed]
  20. Involvement of MAP kinase cascades in Smad7 transcriptional regulation. Uchida, K., Suzuki, H., Ohashi, T., Nitta, K., Yumura, W., Nihei, H. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  21. SMAD2 and SMAD7 involvement in the post-translational regulation of Muc4 via the transforming growth factor-beta and interferon-gamma pathways in rat mammary epithelial cells. Soto, P., Price-Schiavi, S.A., Carraway, K.L. J. Biol. Chem. (2003) [Pubmed]
  22. JinSanE Decoction, A Chinese Herbal Medicine, Inhibits Expression of TGF-beta1/Smads in Experimental Hepatic Fibrosis in Rats. Song, S.L., Gong, Z.J., Huang, Y.Q., Zhang, Q.R., Huang, T.X. Am. J. Chin. Med. (2006) [Pubmed]
  23. Expression and localization of the transforming growth factor-beta type I receptor and Smads in preneoplastic lesions during chemical hepatocarcinogenesis in rats. Park, d.o. .Y., Lee, C.H., Sol, M.Y., Suh, K.S., Yoon, S.Y., Kim, J.W. J. Korean Med. Sci. (2003) [Pubmed]
  24. Tetrandrine inhibits activation of rat hepatic stellate cells in vitro via transforming growth factor-beta signaling. Chen, Y.W., Wu, J.X., Chen, Y.W., Li, D.G., Lu, H.M. World J. Gastroenterol. (2005) [Pubmed]
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