Intercellular crosstalk of hepatic stellate cells in liver fibrosis: New insights into therapy

Liver fibrosis is a dynamic wound-healing process characterized by the net accumulation of extracellular matrix. There is no efficient antifibrotic therapy other than liver transplantation to date. Activated hepatic stellate cells (HSCs) are the major cellular source of matrix-producing myofibroblasts, playing a central role in the initiation and progression of liver fibrosis. Paracrine signals from resident and inflammatory cells such as hepatocytes, liver sinusoidal endothelial cells, hepatic macrophages, natural killer/natural killer T cells, biliary epithelial cells, hepatic progenitor cells, and platelets can directly or indirectly regulate HSC differentiation and activation. Intercellular crosstalk between HSCs and those “responded” cells has been a critical event involved in HSC activation and fibrogenesis. This review summarizes recent advancement regarding intercellular communication between HSCs and other “responded cells” during liver fibrosis and experimental models of intercellular crosstalk systems, and provides novel ideas for potential antifibrotic therapeutic strategy.