Thiol redox systems and protein kinases in hepatic stellate cell regulatory processes

Abstract

Hepatic stellate cells (HSC) are the major producers of collagen in the liver and their conversion from resting cells to a proliferating, contractile and fibrogenic phenotype (‘activation’) is a critical step, leading to liver fibrosis characterized by deposition of excessive extracellular matrix. Cytokines, growth factors, reactive oxygen and nitrogen species (ROS/RNS), lipid peroxides and their products deriving from hepatocytes, Kupffer cells and other cells converge on HSC and influence their activation. This review focuses on glutathione and thioredoxin pathways, with particular emphasis on their role in HSC. These two systems have been shown to act in the metabolism of hydrogen peroxide, control of thiol redox balance and regulation of signalling pathways. Particular attention is paid to mitochondria and NADPH oxidase. Detailed knowledge of specific signalling, redox conditions and apoptotic processes will be of help in devising proper pharmacological treatments for liver fibrosis.