Endoglin Upregulation in the Liver after Bile Duct Ligation in Rats

Background: Transforming growth factor beta 1 (TGF- 1) has been implicated in the stimulation of extracellu- lar matrix synthesis in acute and chronic liver disease. Endoglin (CD-105) is a membrane glycoprotein that binds TGF- 1 with high affinity. Endoglin is overexpressed in several model of fibrosis. The goal of the present study was to evaluate the effect of bile duct ligation (BDL) on endoglin expression and the effect of endoglin overexpression on liver fibrosis in rats. Methods: Rat livers were transfected with a vector containing full length human endoglin (h-end) or an empty vector (mock) and 48 hours after were subjected to either BDL or sham operation (SO). Eighteen days after, a blood sample was obtained and bilirubin and serum enzyme activities were measured to assess liver damage. Liver fibrosis was quantified by a computer-assisted image analysis of Sirius red stained livers and by liver hydroxyproline content. Endoglin expres- sion in the liver tissue was assessed by Western blot and immunohystochemistry. Results: Both immunohistochemistry and Western blot reveals endoglin upregulation after BDL in rats. In addition, these techniques also reveal effective human endoglin transfection in the rat's liver. After BDL, liver fibrosis and plasma levels of enzymes were similar in h-end transfected and mock-transfected rats. Western blots showed higher endoglin expression after BDL in h-end transfected and mock-transfected rats. Conclusions: The present study provides clear evidence that endoglin is upregulated in the liver of rats with BDL. h-end overexpression did not improve liver fibrosis after BDL in rats.