Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress.

Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting. Loss of c-Met signaling amplified the extent of liver injury in MetKO mice fed with high-cholesterol diet for 30days as evidenced by upregulation of liver enz…

Hepatocyte growth factor induces a protective effect in cerulein-induced acute pancreatitis in mice

Redox Regulation by HGF/c-Met in Liver Disease

Reactive oxygen species (ROS) have gained considerable attention in recent years because of their direct involvement in the regulation of multiple physiological and pathological processes. Under normal conditions, ROS have an important role in cell signaling and function as essential mediators of cell homeostasis. However, imbalance between ROS and antioxidant systems induces oxidative stress, which leads to cell and tissue damage. The cellular redox modulation by hepatocyte growth factor (HGF) and its receptor c-Met in the liver has been studied extensively in the past. The generation of liver-specific c-Met–knockout mice has allowed to demonstrate the fundamental importance of HGF/c-Met i…