Association of Transforming Growth Factor-β1 and α-Smooth Muscle Actin in Experimental Selective Obstructive Cholestasis.

Abstract

BACKGROUND/AIM: Hepatic bile duct obstruction is a common cause of cholestasis. In cases of persistent obstruction, fibrosis and cirrhosis occur. A detailed analysis of fibrogenesis will allow the treatment for this condition to be refined and outcomes to be improved. We assessed the induction of fibrosis in selective obstructive cholestasis by determining the expression of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-β1). MATERIALS AND METHODS: Selective bile duct ligation of two of four hepatic lobes was performed in rats. α-SMA and TGF-β1 expression was assessed at 30 days by immunohistochemistry, and hepatic fibrosis was quantified. The expression levels of the two markers were graded and compared, while the correlation with fibrosis was tested. Descriptive and inferential statistical tests were performed. RESULTS: At 30 days, a pre-fibrotic stage was reached. Marker expression was identified in both obstructed and unobstructed parenchyma, with higher expression in the obstructed tissue. TGF-β1 had a more intense expression, and α-SMA expression was significantly correlated with fibrosis. Ito cells showed the highest level of expression. CONCLUSION: Fibrogenesis appears to be initiated in all liver parenchyma early after the induction of cholestasis. α-SMA expression is highly correlated with the degree of fibrosis. A long-term evaluation of the model should be performed for better characterization.