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Gene Review

Smad1  -  SMAD family member 1

Rattus norvegicus

Synonyms: MAD homolog 1, Mad1, Madh1, Mothers against DPP homolog 1, Mothers against decapentaplegic homolog 1, ...
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Disease relevance of Smad1

  • Recently, we showed that the overexpression of type IV collagen (Col IV), a major component of mesangial extracellular matrix, is transcriptionally regulated by Smad1 in diabetic glomerulosclerosis [1].
  • These data suggest that the activation of STAT3 and Smad1 participates in the developing process of glomerulosclerosis in experimental glomerulonephritis [1].
  • In this study, we investigated the regulation of Smad proteins in the glomeruli of rats with anti-thymocyte serum nephritis [2].
  • However, changes in the Smad proteins during the progression of kidney disease are unclear [2].
  • We examined whether alphaT treatment induces prevention of renal insufficiency and fibrosis, and affects the TGF-beta/Smad signaling pathway in rats with chronic progressive anti-thymocyte serum (ATS) nephritis induced by repeated ATS injections on days 0 and 7 [3].

High impact information on Smad1


Chemical compound and disease context of Smad1


Biological context of Smad1

  • In cerebellar cultures prepared at P6 or P10, BMP4 activates Smad1 signaling to modulate cell differentiation [11].
  • Using internal deletions of the promoter, we defined a region between -2,841 to -1,941, which includes the NIS upstream enhancer (NUE), as responsible for the TGF-beta/Smad inhibitory effect [12].
  • A variety of Smad chimera constructs were generated and used in transient transfection studies to address this question [13].
  • Our findings show a colocalization of the pathway-restricted and inhibitory Smads with activating ligands or ligands whose action they antagonize and their receptors in various zones of epiphyseal growth plate, suggesting that TGF-beta superfamily Smad signaling pathways plays a morphogenic role during endochondral bone formation [14].
  • Although the Smad family proteins are critical components of the TGF-beta signaling pathways, the roles of Smad3 in the expression of osteoblastic phenotypes remain poorly understood [15].

Anatomical context of Smad1

  • Expression and localization of Smad1, Smad2 and Smad4 proteins in rat testis during postnatal development [16].
  • For example, Smad1 and Smad5 were highly expressed in proliferating chondrocytes and in those chondrocytes that are undergoing maturation [14].
  • Here, we examined the expression of Smad1 to Smad7 proteins during endochondral ossification of epiphyseal plate of growing rats using immunohistochemical techniques [14].
  • BMP antagonist Noggin blocked the elevation of phosphorylated Smad1 and the expression of Hes1 as well as reducing the percentage of astrocytic SVZ progenitor cells [17].
  • We tested the effects of the ectopic expression of inhibitory Smads in cultured rat smooth muscle cells (SMC) to identify the role of TGF-beta/Smad signaling on the phenotypic modulation of SMC [18].

Associations of Smad1 with chemical compounds


Regulatory relationships of Smad1


Other interactions of Smad1

  • These findings in vivo and in culture suggest that BMP4 and Smad1 signaling participate in regulating postnatal cerebellar differentiation [11].
  • RESULTS: Smad1, Smad2 and Smad4 were present throughout testicular development [16].
  • The immunostaining of Smad1 and Smad2 were present in spermatogenic cells [16].
  • Signaling by bone morphogenetic proteins and Smad1 modulates the postnatal differentiation of cerebellar cells [11].
  • Together, these experiments demonstrate that NO by induction of the Smad signaling pathway modulates TIMP-1 expression [26].

Analytical, diagnostic and therapeutic context of Smad1


  1. Activation of STAT3/Smad1 is a key signaling pathway for progression to glomerulosclerosis in experimental glomerulonephritis. Takahashi, T., Abe, H., Arai, H., Matsubara, T., Nagai, K., Matsuura, M., Iehara, N., Yokode, M., Nishikawa, S., Kita, T., Doi, T. J. Biol. Chem. (2005) [Pubmed]
  2. 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]
  3. 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]
  4. TGF-{beta}1 activates two distinct type I receptors in neurons: implications for neuronal NF-{kappa}B signaling. König, H.G., Kögel, D., Rami, A., Prehn, J.H. J. Cell Biol. (2005) [Pubmed]
  5. Regulation of transforming growth factor beta- and activin-induced transcription by mammalian Mad proteins. Chen, Y., Lebrun, J.J., Vale, W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. Bone morphogenetic protein 4 mediates apoptosis of capillary endothelial cells during rat pupillary membrane regression. Kiyono, M., Shibuya, M. Mol. Cell. Biol. (2003) [Pubmed]
  7. 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]
  8. 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]
  9. Effects of Chinese traditional compound, JinSanE, on expression of TGF-beta1 and TGF-beta1 type II receptor mRNA, Smad3 and Smad7 on experimental hepatic fibrosis in vivo. Song, S.L., Gong, Z.J., Zhang, Q.R., Huang, T.X. World J. Gastroenterol. (2005) [Pubmed]
  10. Angiotensin II activates the Smad pathway in vascular smooth muscle cells by a transforming growth factor-beta-independent mechanism. Rodríguez-Vita, J., Sánchez-López, E., Esteban, V., Rupérez, M., Egido, J., Ruiz-Ortega, M. Circulation (2005) [Pubmed]
  11. Signaling by bone morphogenetic proteins and Smad1 modulates the postnatal differentiation of cerebellar cells. Angley, C., Kumar, M., Dinsio, K.J., Hall, A.K., Siegel, R.E. J. Neurosci. (2003) [Pubmed]
  12. The functional interaction between the paired domain transcription factor Pax8 and Smad3 is involved in transforming growth factor-beta repression of the sodium/iodide symporter gene. Costamagna, E., García, B., Santisteban, P. J. Biol. Chem. (2004) [Pubmed]
  13. Smad3 mediates activin-induced transcription of follicle-stimulating hormone beta-subunit gene. Suszko, M.I., Balkin, D.M., Chen, Y., Woodruff, T.K. Mol. Endocrinol. (2005) [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. Smad3 promotes alkaline phosphatase activity and mineralization of osteoblastic MC3T3-E1 cells. Sowa, H., Kaji, H., Yamaguchi, T., Sugimoto, T., Chihara, K. J. Bone Miner. Res. (2002) [Pubmed]
  16. Expression and localization of Smad1, Smad2 and Smad4 proteins in rat testis during postnatal development. Hu, J., Zhang, Y.Q., Liu, X.P., Wang, R.A., Jin, Y., Xu, R.J. Asian J. Androl. (2003) [Pubmed]
  17. Bone marrow stromal cells induce BMP2/4 production in oxygen-glucose-deprived astrocytes, which promotes an astrocytic phenotype in adult subventricular progenitor cells. Xin, H., Li, Y., Chen, X., Chopp, M. J. Neurosci. Res. (2006) [Pubmed]
  18. 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]
  19. 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]
  20. Expression and localization of activin receptors, Smads, and beta glycan to the postnatal rat ovary. Drummond, A.E., Le, M.T., Ethier, J.F., Dyson, M., Findlay, J.K. Endocrinology (2002) [Pubmed]
  21. Activation of TGF-beta-Smad signaling pathway following polyamine depletion in intestinal epithelial cells. Liu, L., Santora, R., Rao, J.N., Guo, X., Zou, T., Zhang, H.M., Turner, D.J., Wang, J.Y. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  22. Peptide YY attenuates transcription factor activity in tumor necrosis factor-alpha-induced pancreatitis. Vona-Davis, L., Yu, A., Magabo, K., Evans, T., Jackson, B., Riggs, D., McFadden, D. J. Am. Coll. Surg. (2004) [Pubmed]
  23. Sphingosine 1-phosphate cross-activates the Smad signaling cascade and mimics transforming growth factor-beta-induced cell responses. Xin, C., Ren, S., Kleuser, B., Shabahang, S., Eberhardt, W., Radeke, H., Schäfer-Korting, M., Pfeilschifter, J., Huwiler, A. J. Biol. Chem. (2004) [Pubmed]
  24. Bone morphogenetic protein-2 inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of the Smad1 pathway. Izumi, M., Fujio, Y., Kunisada, K., Negoro, S., Tone, E., Funamoto, M., Osugi, T., Oshima, Y., Nakaoka, Y., Kishimoto, T., Yamauchi-Takihara, K., Hirota, H. J. Biol. Chem. (2001) [Pubmed]
  25. Cross-talk between the Smad1 and Ras/MEK signaling pathways for TGFbeta. Yue, J., Frey, R.S., Mulder, K.M. Oncogene (1999) [Pubmed]
  26. Nitric oxide induces TIMP-1 expression by activating the transforming growth factor beta-Smad signaling pathway. Akool, e.l.-.S., Doller, A., Müller, R., Gutwein, P., Xin, C., Huwiler, A., Pfeilschifter, J., Eberhardt, W. J. Biol. Chem. (2005) [Pubmed]
  27. Activation of the Smad pathway in glomeruli from a spontaneously diabetic rat model, OLETF rats. Furuse, Y., Hashimoto, N., Maekawa, M., Toyama, Y., Nakao, A., Iwamoto, I., Sakurai, K., Suzuki, Y., Yagui, K., Yuasa, S., Toshimori, K., Saito, Y. Nephron Exp. Nephrol. (2004) [Pubmed]
  28. 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]
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