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Am J Physiol Gastrointest Liver Physiol (June 4, 2003). doi:10.1152/ajpgi.00436.2002
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Submitted on October 10, 2002
Accepted on May 23, 2003

Transforming growth factor beta1 down-regulation of Smad1 gene expression in rat hepatic stellate cells

Hong Shen1, Guojiang Huang2, Mohammed Hadi3, Patrick Choy3, Manna Zhang2, Gerald Y. Minuk2, Yongping Chen1, and Yuewen Gong4*

1 Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada
2 Department of Internal Medicine, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada
3 Department of Biochemistry and Medical Genetics, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada
4 Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada; Department of Internal Medicine, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada

* To whom correspondence should be addressed. E-mail: ygong{at}ms.umanitoba.ca.

Smads are intracellular signaling molecules of the transforming growth factor beta (TGF-{beta}) superfamily which play an important role in the activation of hepatic stellate cells and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat hepatic stellate cells 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 hepatic stellate cells. Moreover, TGF-{beta}1 significantly inhibits Smad1 gene expression in hepatic stellate cells in a time and dose dependent manner. Furthermore, while both TGF-{beta}1 and BMP2 stimulate the activation of hepatic stellate cells they have different effects on hepatic stellate cell proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of hepatic stellate cells and TGF-{beta}1 significantly inhibits the expression of the Smad1 gene.




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