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HORMONES AND SIGNALING

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

¹Faculty of Pharmacy and Departments of ²Biochemistry and Medical Genetics and ³Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada

Submitted 10 October 2002 ; accepted in final form 23 May 2003

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, TGF- significantly inhibits Smad1 gene expression in HSCs in a time- and dose-dependent manner. Furthermore, although both TGF-1 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 TGF-1 significantly inhibits the expression of the Smad1 gene.

transforming growth factor-; Smad1; regulation

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