Expression of fibronectin receptor, integrin alpha(5)beta(1) of hepatic stellate cells in rat liver fibrosis

Objective to investigate the role of fibronectin(FN) receptor alpha(5)beta( 1) in liver fibrosis. Methods Northem bllot analysis and immunohistochemical observe changes in t he expression of FN and FN receptor alpha(5)beta(1) on hepatic stellate cel ls (HSCs) in vivo and in vitro of rat liver fibrosis induced by CCl4. Results (1) alpha(5)beta(1) was mainly detected in the endothelia and some of the desmin( DM) positive cells of the sinusoids in normal rat liver. The expression of alpha(5)beta(1), of DM positive cells detected by immunohist ochemistry reached its peak at the 10th week of the experiment. The changes in FN expression were similar to that of alpha(5)beta(1) (2) The expressio n of FN, alpha(5) and beta(1) mRNAs in the experimental group was remarkabl y increased especially at the 6th week, compared to that of normal liver sp ecimens. The expression of the three mRNAs of HSCs in vitro isolated from t he experimental group (6 weeks) was higher than those from normal liver. (3 ) The expression of FN, alpha(5) and beta(1) mRNAs increased in normal rat HSCs after treatment with transforming growth factor-beta(1) (TGF-beta(1)) for 2 hours. After 4 hours of treatment, the expression of the three mRNAs fell to levels similar to the control group. Immunocytochemistry revealed t hat the expression of alpha(5)beta(1), of HSCs reached its peak after 4 hou rs of treatment with TGF-beta(1) and dropped to normal 2 hours later. Conclusion These data suggest that HSCs normally express RU receptor alpha( 5)beta(1) The activation of HSCs during liver fibrogenesis leads to an incr ease of FN, cg and beta(1) mRNA expression. The expression of FN and alpha( 5)beta(1) of HSCs in vitro is up-regulated by TFG-alpha(5)beta(1). The dete ction of gene transcription of FN and its receptor by Northern blot analysi s suggests the activation and proliferation of HSCs and thereby provides a sensitive signal of liver fibrosis.