Liver fibrosis is the common scarring reaction associated with chronic liver injury that results from prolonged parenchymal cell injury and/or inflammation. The fibrogenic response is characterized by progressive accumulation of extracellular matrix components enriched in fibrillar collagens and a failure of matrix turnover. This process is driven by a heterogenous population of hepatic myofibroblasts, that mainly derive from hepatic stellate cells and portal fibroblasts. Regression of fibrosis can be achieved by the successful control of chronic liver injury, owing to termination of the fibrogenic reaction following clearance of hepatic myofibroblasts and restoration of fibrolytic pathways. Understanding of the complex network underlying liver fibrogenesis has allowed the identification of a large number of antifibrotic targets, but no antifibrotic drug has as-yet been approved. This review will highlight recent advances regarding the mechanisms rthat regulate liver fibrogenesis and fibrosis regression, with special focus on novel signalling pathways and the role of inflammatory cells. Translation of these findings to therapies will require continued efforts to develop multi-target therapeutic approaches that will improve the grim prognosis of liver cirrhosis.
- hepatic stellate cells
- chronic liver disease
- Copyright © 2013, American Journal of Physiology - Cell Physiology