Induction of tropomyosin during hepatic stellate cell activation and the progression of liver fibrosis.

The activation of hepatic stellate cells (HSCs) is a cue to initiate liver fibrosis. Activated stellate cells acquire contractile activity similar to pericytes and myofibroblasts in other organs by inducing the contractile machinery of cytoskeletons such as smooth muscle alpha-actin (alpha-SMA), a well-known marker of activated stellate cells, and actin-binding proteins. We further show herein the expression of tropomyosin in rat HSCs in the course of their activation during primary culture and liver tissue damaged by thioacetamide intoxication. In immunoblot analysis, tropomyosin became detectable in an early stage of the primary culture of rat stellate cells in a manner similar to the expression of alpha-SMA and platelet-derived growth factor receptor-beta. Tropomyosin was found to be colocalized with alpha-SMA on fluorescent immunocytochemistry. At the liver tissue level, an increased expression of tropomyosin was observed by immunoblot analysis and immunohistochemistry along the septum of fibrosis, where alpha-SMA was enriched. These results strongly suggest that tropomyosin is a new marker of activated stellate cells and may serve as a useful diagnostic marker of liver fibrosis.