Figure 1.

Mechanisms of biliary damage during cholestasis. Bile duct ligation (BDL) induces the proliferation of cholangiocytes, which is associated with increased cAMP-dependent signaling mechanisms. Cholestasis induced by BDL renders cholangiocytes more sensitive to damage by hepatotoxins, hepatic artery ligation (HAL) and denervation. This damage is associated with increased cholangiocyte apoptosis and decreased cAMP-dependent signaling mechanisms. Administration of cAMP agonists (for CCl₄ and denervation), VEGF-A (for HAL), and TC (for HAL and denervation) have been shown to restore cholangiocyte proliferation and cAMP dependent signaling mechanisms and prevent cholangiocyte apoptosis.