title: Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches.
abstract: The pathogenesis of hepatic fibrosis involves significant deposition of fibrilar collagen and other extracellular matrix proteins. It is a rather dynamic process of wound healing in response to a variety of persistent liver injury caused by factors such as ethanol intake, viral infection, drugs, toxins, cholestasis, and metabolic disorders. Liver fibrosis distorts the hepatic architecture, decreases the number of endothelial cell fenestrations and causes portal hypertension. Key events are the activation and transformation of quiescent hepatic stellate cells into myofibroblast-like cells with the subsequent up-regulation of proteins such as α-smooth muscle actin, interstitial collagens, matrix metalloproteinases, tissue inhibitor of metalloproteinases, and proteoglycans. Oxidative stress is a major contributing factor to the onset of liver fibrosis and it is typically associated with a decrease in the antioxidant defense. Currently, there is no effective therapy for advanced liver fibrosis. In its early stages, liver fibrosis is reversible upon cessation of the causative agent. In this review, we discuss some aspects on the etiology of liver fibrosis, the cells involved, the molecular pathogenesis, and the current therapeutic approaches.
authors.affiliation: Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, NY 10029, USA.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mormone
authors.forename: Joseph
authors.initials: J
authors.lastname: George
authors.forename: Natalia
authors.initials: N
authors.lastname: Nieto
mesh_terms: D015316:Genetic Therapy; D055166:Hepatic Stellate Cells / Q000166:cytology; D006519:Hepatitis, Alcoholic / Q000150:complications / Q000473:pathology; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000628:therapy; D020782:Matrix Metalloproteinases / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism / Q000627:therapeutic use; D018384:Oxidative Stress; D034622:RNA Interference
chemical_list: D035683:MicroRNAs; D020782:Matrix Metalloproteinases