Inactivation of myofibroblasts during regression of liver fibrosis

Hepatic fibrosis results from many chronic liver diseases, including hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease and non-alcoholic steatohepatitis (NASH). Hepatic fibrosis is the scar caused by deregulation of physiological wound healing and results in excessive production of extracellular matrix (ECM), mostly collagen type I. Myofibroblasts, which are not present in normal liver, are the major source of the ECM during fibrogenesis. Activation and proliferation of hepatic myofibroblasts are required for the development of fibrosis. Myofibroblasts are characterized by stellate shape, expression of abundant intracellular filaments [α-smooth muscle actin (α-SMA), vimentin], high contractility and secretion of ECM (fibronectin, collagen type I and III). Hepatic stellate cells (HSCs) are the major source of myofibroblasts in hepatotoxic liver fibrosis. Under physiological conditions, HSCs reside in the space of Disse and exhibit a quiescent phenotype (qHSCs). They express neural markers, such as GFAP, synemin, synaptophysin and nerve growth factor receptor p75, and store vitamin A in lipid droplets. In response to injury, qHSCs decrease vitamin A storage and peroxisome proliferator-activated receptor gamma (PPARγ) expression and activate into collagen type Iand α-SMA-expressing myofibroblasts. Although the mechanism of HSC activation has been comprehensively studied, Inactivation of myofibroblasts during regression of liver fibrosis