Oxidative Stress and Liver Fibrogenesis

Abstract

AbstractLiver fibrogenesis is a dynamic and highly integrated molecular and cellular process, involving the whole tissue and potentially reversible, which drives the progression of chronic liver diseases (CLD) first towards liver fibrosis (i.e., the “result” of fibrogenesis) and eventually towards liver cirrhosis and hepatic failure. Hepatic myofibroblasts (MFs), whatever their origin, are major pro-fibrogenic cells that also represent a critical cellular crossroads able to represent both a source and a target for mediators involved in CLD progression. Oxidative stress, reactive oxygen species (ROS), and redox signalling are believed to play a critical role in the process of activation of MFs as well as in mediating or modulating the phenotypic responses of activated MFs. In particular, hepatic MFs respond to a sustained increase in intracellular levels of ROS or other oxidative stress-related mediators of extracellular origin (i.e., released by damaged hepatocytes or activated inflammatory cells) as well as to a raise in ROS levels that follows exposure to either hypoxic conditions or to several critical polypeptides leading, through ligand–receptor interaction, to activation of NADPH oxidase (NOX) activity.KeywordsHepatic stellate cellsHepatic myofibroblastsFibrogenesisChronic liver diseaseCirrhosisOxidative stressReactive oxygen speciesRedox signallingHypoxiaHypoxia-inducible factorsNADPH-oxidaseAntioxidants