Molecular Mechanism of Stellate Cell Activation and Extracellular Matrix Remodeling

In normal liver, hepatic stellate cells are perisinusoidal vitamin A-storing cells located in the subendothelial space of Disse. Following liver injury, they undergo a spectrum of phenotypic changes and transform into proliferative, fibrogenic, and contractile myofibroblasts-a process collectively termed as "activation." This chapter reviews the biological characteristics of hepatic stellate cells and addresses their functions in injured liver, with special emphasis on the molecular mechanisms of stellate cell activation. In normal liver, stellate cells play a major role in maintaining hepatic homeostasis. Their main functions include production of cytokines and other mediators, expression of membrane receptors, cell matrix synthesis and degradation, regulation of hepatic sinusoidal blood flow through their contractility, and retinoid storage and metabolism. One of the main features of hepatic stellate cells is their versatility in producing a rich array of cytokines in the liver. Signal transduction mediated by binding of cytokines to their membrane receptors comprises the main mode of cell-cell interaction in both normal and injured liver. The fate of activated stellate cells during the resolution of liver injury needs to be clarified, and more importantly, the factors that determine the reversibility of liver fibrosis must be identified.