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Gene Review

Smad2  -  SMAD family member 2

Rattus norvegicus

Synonyms: MAD homolog 2, Mad-related protein 2, Madh2, Mothers against DPP homolog 2, Mothers against decapentaplegic homolog 2, ...
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Disease relevance of Smad2


High impact information on Smad2

  • Transforming growth factor beta1 signaling in cholangiocytes in vivo was evident by increased phosphorylation and nuclear localization of Smad2, and hepatic endothelin 1 levels correlated directly with liver transforming growth factor beta1 and phosphorylated Smad2 levels [6].
  • Treatment with CM(Cerebellum) caused nuclear translocation of SMAD2 and SMAD4, and also transactivated a TGFbeta2-responsive gene [7].
  • Thereafter, Smad 7 induced by TGF-beta negatively regulated the Smad 2 action [8].
  • Subpopulations of Smad2/Smad3-positive and apoptotic nuclei colocalized, indicating a role for Smads in apoptosis [9].
  • Smad3-overexpressing cells exhibited increased deposition of fibronectin and type 1 collagen, increased chemotaxis, and decreased proliferation compared with uninfected cells and those infected with Smad2 or either dominant negative, demonstrating different biological functions for the two Smads [10].

Chemical compound and disease context of Smad2


Biological context of Smad2


Anatomical context of Smad2


Associations of Smad2 with chemical compounds


Regulatory relationships of Smad2


Other interactions of Smad2


Analytical, diagnostic and therapeutic context of Smad2

  • In prostatic tumor cells we observed an increased expression of Smad2 and P-Smad2 after treatment [20].
  • To decipher the mechanism of TGF-beta signaling during the estrous cycle and implantation, we performed in situ hybridization to investigate the expression patterns of mRNAs for Smad2 and Smad4 in rat endometrium during the estrous cycle and on Days 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 of pregnancy [12].
  • The ability of Smad7 to block Smad2/3 activation and attenuate renal and vascular sclerosis demonstrates that ultrasound-mediated Smad7 gene therapy may be a useful therapeutic strategy for the prevention of renal fibrosis in association with hypertension [27].
  • However, TGFbeta2-mediated calcium current reductions were prevented by intracellular perfusion of a Smad2/3 peptide antagonist [28].
  • Semi-quantitative RT-PCR revealed reduced expression of TGF-betaRII in 2 HCCs (16.7%) without Smad2 mutations out of 12 HCCs induced by the CDAA diet and none of 11 induced by DEN [29].


  1. Ubiquitin-dependent degradation of Smad2 is increased in the glomeruli of rats with anti-thymocyte serum nephritis. Togawa, A., Yamamoto, T., Suzuki, H., Fukasawa, H., Ohashi, N., Fujigaki, Y., Kitagawa, K., Hattori, T., Kitagawa, M., Hishida, A. Am. J. Pathol. (2003) [Pubmed]
  2. Regulation of Smad3 expression in bleomycin-induced pulmonary fibrosis: a negative feedback loop of TGF-beta signaling. Zhao, Y., Geverd, D.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  3. Smad2 overexpression enhances Smad4 gene expression and suppresses CBFA1 gene expression in osteoblastic osteosarcoma ROS17/2.8 cells and primary rat calvaria cells. Li, J., Tsuji, K., Komori, T., Miyazono, K., Wrana, J.L., Ito, Y., Nifuji, A., Noda, M. J. Biol. Chem. (1998) [Pubmed]
  4. Mutations of the Smad2 and Smad4 genes in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. Tsujiuchi, T., Sasaki, Y., Tsutsumi, M., Konishi, Y. Mol. Carcinog. (2000) [Pubmed]
  5. Angiotensin-converting enzyme inhibitors: a new mechanism of action. Peng, H., Carretero, O.A., Vuljaj, N., Liao, T.D., Motivala, A., Peterson, E.L., Rhaleb, N.E. Circulation (2005) [Pubmed]
  6. Cholangiocyte endothelin 1 and transforming growth factor beta1 production in rat experimental hepatopulmonary syndrome. Luo, B., Tang, L., Wang, Z., Zhang, J., Ling, Y., Feng, W., Sun, J.Z., Stockard, C.R., Frost, A.R., Chen, Y.F., Grizzle, W.E., Fallon, M.B. Gastroenterology (2005) [Pubmed]
  7. SMAD pathway mediation of BDNF and TGF beta 2 regulation of proliferation and differentiation of hippocampal granule neurons. Lu, J., Wu, Y., Sousa, N., Almeida, O.F. Development (2005) [Pubmed]
  8. Differential regulation of TGF-beta signal in hepatic stellate cells between acute and chronic rat liver injury. Tahashi, Y., Matsuzaki, K., Date, M., Yoshida, K., Furukawa, F., Sugano, Y., Matsushita, M., Himeno, Y., Inagaki, Y., Inoue, K. Hepatology (2002) [Pubmed]
  9. Activation of the transforming growth factor beta signaling pathway and induction of cytostasis and apoptosis in mammary carcinomas treated with the anticancer agent perillyl alcohol. Ariazi, E.A., Satomi, Y., Ellis, M.J., Haag, J.D., Shi, W., Sattler, C.A., Gould, M.N. Cancer Res. (1999) [Pubmed]
  10. Smad2 and Smad3 play different roles in rat hepatic stellate cell function and alpha-smooth muscle actin organization. Uemura, M., Swenson, E.S., Gaça, M.D., Giordano, F.J., Reiss, M., Wells, R.G. Mol. Biol. Cell (2005) [Pubmed]
  11. Transforming growth factor beta (TGF-beta) signaling is regulated by electrical activity in skeletal muscle cells. TGF-beta type I receptor is transcriptionally regulated by myotube excitability. Ugarte, G., Brandan, E. J. Biol. Chem. (2006) [Pubmed]
  12. Expression of Smad2 and Smad4, transforming growth factor-beta signal transducers in rat endometrium during the estrous cycle, pre-, and peri-implantation. Lin, H.Y., Wang, H.M., Li, Q.L., Liu, D.L., Zhang, X., Liu, G.Y., Qian, D., Zhu, C. Anim. Reprod. Sci. (2004) [Pubmed]
  13. 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]
  14. The Effects of Different Immunosuppressants on Chronic Allograft Nephropathy by Affecting the Transforming Growth Factor-beta and Smads Signal Pathways. Gao, R., Lu, Y., Xin, Y.P., Zhang, X.H., Wang, J., Li, Y.P. Transplant. Proc. (2006) [Pubmed]
  15. Smads 2 and 3 are differentially activated by transforming growth factor-beta (TGF-beta ) in quiescent and activated hepatic stellate cells. Constitutive nuclear localization of Smads in activated cells is TGF-beta-independent. Liu, C., Gaça, M.D., Swenson, E.S., Vellucci, V.F., Reiss, M., Wells, R.G. J. Biol. Chem. (2003) [Pubmed]
  16. 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]
  17. Treatment with anti-TGF-beta antibody ameliorates chronic progressive nephritis by inhibiting Smad/TGF-beta signaling. Fukasawa, H., Yamamoto, T., Suzuki, H., Togawa, A., Ohashi, N., Fujigaki, Y., Uchida, C., Aoki, M., Hosono, M., Kitagawa, M., Hishida, A. Kidney Int. (2004) [Pubmed]
  18. Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor-gamma, transforming growth factor-beta1, and a Smad2-dependent mechanism. Redondo, S., Ruiz, E., Santos-Gallego, C.G., Padilla, E., Tejerina, T. Diabetes (2005) [Pubmed]
  19. In vivo inosine protects alveolar epithelial type 2 cells against hyperoxia-induced DNA damage through MAP kinase signaling. Buckley, S., Barsky, L., Weinberg, K., Warburton, D. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  20. 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]
  21. Extracellular signal regulated kinase and SMAD signaling both mediate the angiotensin II driven progression towards overt heart failure in homozygous TGR(mRen2)27. Boer, R.A., Pokharel, S., Flesch, M., van Kampen, D.A., Suurmeijer, A.J., Boomsma, F., van Gilst, W.H., van Veldhuisen, D.J., Pinto, Y.M. J. Mol. Med. (2004) [Pubmed]
  22. Growth differentiation factor-9 stimulates inhibin production and activates Smad2 in cultured rat granulosa cells. Roh, J.S., Bondestam, J., Mazerbourg, S., Kaivo-Oja, N., Groome, N., Ritvos, O., Hsueh, A.J. Endocrinology (2003) [Pubmed]
  23. Transforming growth factor-beta 1 regulation of collagenase-3 expression in osteoblastic cells by cross-talk between the Smad and MAPK signaling pathways and their components, Smad2 and Runx2. Selvamurugan, N., Kwok, S., Alliston, T., Reiss, M., Partridge, N.C. J. Biol. Chem. (2004) [Pubmed]
  24. TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions. Mori, S., Matsuzaki, K., Yoshida, K., Furukawa, F., Tahashi, Y., Yamagata, H., Sekimoto, G., Seki, T., Matsui, H., Nishizawa, M., Fujisawa, J., Okazaki, K. Oncogene (2004) [Pubmed]
  25. Transforming growth factor-beta and platelet-derived growth factor signal via c-Jun N-terminal kinase-dependent Smad2/3 phosphorylation in rat hepatic stellate cells after acute liver injury. Yoshida, K., Matsuzaki, K., Mori, S., Tahashi, Y., Yamagata, H., Furukawa, F., Seki, T., Nishizawa, M., Fujisawa, J., Okazaki, K. Am. J. Pathol. (2005) [Pubmed]
  26. Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. Mazerbourg, S., Klein, C., Roh, J., Kaivo-Oja, N., Mottershead, D.G., Korchynskyi, O., Ritvos, O., Hsueh, A.J. Mol. Endocrinol. (2004) [Pubmed]
  27. 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]
  28. TGFbeta2 mediates rapid inhibition of calcium influx in identified cholinergic basal forebrain neurons. Williams, S., Souchelnytskyi, S., Danik, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  29. Alterations of the transforming growth factor-beta signaling pathway in hepatocellular carcinomas induced endogenously and exogenously in rats. Sasaki, Y., Tsujiuchi, T., Murata, N., Tsutsumi, M., Konishi, Y. Jpn. J. Cancer Res. (2001) [Pubmed]
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