Relationship between focal adhesion kinase and hepatic stellate cell proliferation during rat hepatic fibrogenesis

To investigate the dynamic expression of focal adhesion kinase (FAK) protein and FAK mRNA in fibrotic rat liver tissue, and the relationship between FAK and hepatic stellate cell (HSC) proliferation.

Rat hepatic fibrosis was induced by bile duct ligation (BDL). Histopathological changes were evaluated by hematoxylin and eosin staining, and by Masson's trichrome method. FAK mRNA in the rat livers was determined by reverse transcription-polymerase chain reaction (RT-PCR), and the distributions of FAK were assessed immunohistochemistrically. The number of activated HSCs was quantified after alpha smooth muscle actin (alpha-SMA) staining.

With the development of hepatic fibrosis, the positively stained cells of alpha-SMA increased obviously, which were mainly resided in the portal ducts, fiber septa and perisinuses accompanied with proliferating bile ducts. The positively stained areas of the rat livers in model groups 1 to 4 wk after ligation of common bile duct (12.88+/-2.63%, 22.65+/-2.16%, 27.45+/-1.86%, 35.25+/-2.34%, respectively) were significantly larger than those in the control group (5.88+/-1.46%) (P<0.01). The positive staining for FAK significantly increased, which was mainly situated in portal ducts, fiber septa and around the bile ducts, vascular endothelial cells and perisinusoidal cells. The expression of FAK was positively correlated with alpha-SMA expression (r = 0.963, P<0.05). FAK mRNA expression was obviously up-regulated in the model groups compared to the control group.

These data suggest that expressions of FAK protein and mRNA are greatly increased in fibrotic rat livers, which may play an important role in HSC proliferation and hepatic fibrogenesis.