Transforming growth factor- 1 downregulation of Smad1 gene expression in rat hepatic stellate cells

Shen, Hong, Guojiang Huang, Mohammed Hadi, Patrick Choy, Manna Zhang, Gerald Y. Minuk, Yongping Chen, and Yuewen Gong. Transforming growth factor1 downregulation of Smad1 gene expression in rat hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 285: G539–G546, 2003. First published June 4, 2003; 10.1152/ajpgi.00436.2002.—Smads are intracellular signaling molecules of the transforming growth factor(TGF) superfamily that play an important role in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat HSCs to investigate the expression and regulation of the Smad1 gene, which is a bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the expression and phosphorylation of Smad1 are increased during the activation of HSCs. Moreover, TGFsignificantly inhibits Smad1 gene expression in HSCs in a timeand dose-dependent manner. Furthermore, although both TGF1 and BMP2 stimulate the activation of HSCs, they have different effects on HSC proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of HSCs and TGF1 significantly inhibits the expression of the Smad1 gene.