Role of TGF-β/activin signaling pathway in liver regeneration.

点击翻译按钮获取中文摘要

Transforming growth factor (TGF)-β and activin A inhibit the growth and induce cell death of parenchymal liver cells. Smad proteins have recently been identified as intracellular signaling mediators and modulators of TGF-β family members. This study assessed the role of Smad proteins during the action of TGF-β and activin A on liver cells using a well-differentiated hepatoma cell line, Hep3B cells. To study the role of Smad proteins in the apoptosis-inducing, anti-proliferative activities of TGF-β and activin A in liver cells, we stably transfected dominant negative Smad2-3SA or Smad3-3SA mutants in Hep3B cells. Transfection of Smad2-3SA or Smad3-3SA abrogated both TGF-β-induced and activin A-induced apoptosis and growth inhibition of Hep3B cells. We also demonstrate that transfection of Smad7, an intracellular antagonist of Smad signaling, inhibited both TGF-β- and activin A-induced apoptosis and growth inhibition of these cells. These results suggest that Smad proteins positively and negatively mediate TGF-β-induced and activin A-induced apoptosis and growth inhibition of liver cells.