Fig. 4

Schematic representation of the role of YAP/TAZ in liver regeneration after acute tissue injury. A In YAP /TAZ BEC-KO liver severe degeneration of bile ducts causes cholestasis and has secondary effects on hepatocytes and macrophages, resulting in impaired liver regeneration. More specifically, bile acid overload is responsible for PXR-mediated suppression of cytokine production in hepatocytes, which impairs phagocytic macrophage recruitment and activation. Decreased macrophage function impairs the tissue regeneration process by reducing the clearance of cellular debris from the injury site. B In WILD TYPE liver, injury (2/3 PH)-associated bile acid overload increases osmotic and fluid pressures in the liver, resulting in higher tension of the apical membrane of hepatocytes that form the bile canalicular network. Therefore, YAP, which is localized in the F-actin-rich region of the apical membrane of hepatocytes, is activated. YAP /TAZ positively modulate liver regeneration by promoting the trans-differentiation of hepatocytes to a BEC phenotype thus contributing to liver regeneration through the formation of new bile ducts. YAP: black, inactive; red, active