Hepatic fibrosis and angiogenesis after bile duct ligation are endogenously expressed vasohibin-1 independent

Abstract

Liver fibrosis is linked to VEGF-induced angiogenesis. Overexpression of exogenous vasohibin-1, a feedback inhibitor of angiogenesis, has been reported to reduce liver fibrosis after bile duct ligation (BDL). To uncover the function of endogenous vasohibin-1, we performed BDL using vasohibin-1-deficient mice and analyzed liver fibrosis, injury, and angiogenesis. Liver fibrosis was induced by 14-days of BDL in both wild-type and vasohibin-1-deficient mice. The liver sections were stained with anti-CD31 to visualize endothelial cells and with Sirius red to observe fibrotic regions. Total RNAs were purified from the livers and expression of collagen I α1 mRNA was measured by quantitative PCR. Plasma ALT activity was determined to assess liver injury. Surprisingly, the same extents of increases were seen in anti-CD31 and Sirius red stainings, collagen I α1 mRNA expressions, hepatic hydroxyproline contents, and ALT activity after 14-days of BDL in both wild-type and vasohibin-1-deficient mice. There was unexpectedly no difference between these mice, suggesting that anti-fibrogenic and angiogenic activities of the endogenous vasohibin-1 might be masked in the normal liver at early stage of hepatic fibrosis in mice.

Keywords: Angiogenesis; Bile duct ligation; Fibrosis; Liver; Vasohibin-1.