Regulation of hepatic stellate cells by connective tissue growth factor.

ABSTRACT

Connective tissue growth factor (CTGF/CCN2) regulates cell proliferation, differentiation, adhesion, chemotaxis, migration, apoptosis and extracellular matrix production. Through these diverse actions, CTGF/CCN2 plays a major role in important physiological and pathophysiological processes such as embryogenesis, implantation, angiogenesis, chondrogenesis, tumorigenesis, differentiation, wound healing and fibrosis. Whereas hepatic levels of CTGF/CCN2 are usually low, elevated levels of hepatic CTGF/CCN2 occur in patients with liver fibrosis and in experimental animal models of liver fibrosis. In fibrotic liver, CTGF/CCN2 is produced by multiple cell types but its sustained expression by and action on hepatic stellate cells is particularly important because these cells assume an activated phenotype during fibrosing injury and are principally responsible for the excessive production of fibrillar collagens, a process that is driven by CTGF/CCN2. Through its direct actions and interactions with other molecules such as fibronectin or transforming growth factor beta-1, CTGF/CCN2 promotes proliferation, survival, migration, adhesion, and extracellular matrix production in activated hepatic stellate cells, thereby promoting hepatic fibrogenic pathways. This review focuses on the regulation of hepatic stellate cell function by CTGF/CCN2.