Cellular sources of extracellular matrix in hepatic fibrosis

The deposition of increased and abnormal extracellular matrix is the hallmark of liver fibrosis. Hepatic stellate cells are well known as the major source of the fibrillar collagens and other components of the liver scar, but are now appreciated to be only one of many potentially fibrogenic cell populations in the diseased liver. Portal fibroblasts and circulating mesenchymal cells derived from the bone marrow are also important sources of matrix proteins in fibrosis. Recent data suggest that hepatocytes and biliary epithelial cells undergo an epithelial to mesenchymal transition, similarly assuming a fibrogenic phenotype. Sinusoidal endothelial cells and hepatocytes produce specific matrix proteins important in liver health and disease. The future challenge will be to define more explicitly the roles of these different fibrogenic cell populations in fibrosis in a disease-specific way.