title: The Role of NADPH Oxidases (NOXs) in Liver Fibrosis and the Activation of Myofibroblasts.
abstract: Chronic liver injury, resulted from different etiologies (e.g., virus infection, alcohol abuse, nonalcoholic steatohepatitis (NASH) and cholestasis) can lead to liver fibrosis characterized by the excess accumulation of extracellular matrix (ECM) proteins (e.g., type I collagen). Hepatic myofibroblasts that are activated upon liver injury are the key producers of ECM proteins, contributing to both the initiation and progression of liver fibrosis. Hepatic stellate cells (HSCs) and to a lesser extent, portal fibroblast, are believed to be the precursor cells that give rise to hepatic myofibroblasts in response to liver injury. Although, much progress has been made toward dissecting the lineage origin of myofibroblasts, how these cells are activated and become functional producers of ECM proteins remains incompletely understood. Activation of myofibroblasts is a complex process that involves the interactions between parenchymal and non-parenchymal cells, which drives the phenotypic change of HSCs from a quiescent stage to a myofibroblastic and active phenotype. Accumulating evidence has suggested a critical role of NADPH oxidase (NOX), a multi-component complex that catalyzes reactions from molecular oxygen to reactive oxygen species (ROS), in the activation process of hepatic myofibroblasts. NOX isoforms, including NOX1, NOX2 and NOX4, and NOX-derived ROS, have all been implicated to regulate HSC activation and hepatocyte apoptosis, both of which are essential steps for initiating liver fibrosis. This review highlights the importance of NOX isoforms in hepatic myofibroblast activation and the progression of liver fibrosis, and also discusses the therapeutic potential of targeting NOXs for liver fibrosis and associated hepatic diseases.
authors: Department of Surgery, University of California, San DiegoLa Jolla, CA, USA; Department of Medicine, University of California, San DiegoLa Jolla, CA, USA.
authors: Shuang
authors: S
authors: Liang
authors: Department of Surgery, University of California, San Diego La Jolla, CA, USA.
authors: Tatiana
authors: T
authors: Kisseleva
authors: Department of Medicine, University of California, San Diego La Jolla, CA, USA.
authors: David A
authors: DA
authors: Brenner
keywords: NADPH oxidase (NOX); hepatic stellate cells (HSCs); hepatocytes; liver fibrosis; myofibroblasts; reactive oxygen species (ROS)