Phenotypic Changes in Hepatic Stellate Cells in Response to Toxic Liver Injury

Abstract

Hepatic stellate cells (HSCs) are the main extracellular matrix-producing cell type in the liver. These cells exist in a quiescent state in normal liver and an activated state in damaged liver. During quiescence, HSCs store and release various retinoids. After injury to the liver, however, various protein and non-protein mediators are released from cells that stimulate HSCs to differentiate into myofibroblasts, a process termed activation. Activated HSCs begin to express α-smooth muscle actin and migrate to sites of injury through chemotaxis. Within the damaged region of liver, these cells become contractile and produce growth factors that promote hepatocyte replication and angiogenesis, produce extracellular matrix that forms the scaffold for liver repair, and produce proteins that modulate immune cell function. Once liver repair is complete and liver function is restored, HSCs revert back to a quiescent phenotype or die by apoptosis. If liver injury becomes chronic, however, these processes persist resulting in the formation of an extensive scar (i.e., fibrosis) that ultimately leads to liver failure. Because of the importance of these cells to the development of liver fibrosis, there has been extensive research into understanding the mechanisms that drive HSC activation after injury and the mechanisms that regulate reversion of these cells back to quiescence after resolution of injury. In addition, there has been great interest in identifying the various functions of HSCs after acute and chronic injury. The aim of this review is to briefly discuss the phenotypic changes that occur in HSCs after acute and chronic liver injury and to highlight some of the important functions of these cells during repair of the liver.