Intracellular signaling pathways in stellate cell activation

Pathological fibrogenesis in the liver is mediated by activated stellate ce lls. These cells have a myofibroblastic phenotype with the ability to proli ferate and synthesize large quantities of extracellular matrix components. A number of factors have been proposed to initiate and perpetuate the fibro genic process in stellate cells, including inflammatory cytokines, alterati ons in the extracellular matrix, growth factors, and oxidative stress. Some recent research has focused on the intracellular signaling pathways that a re stimulated by these factors in stellate cells, including mitogen-activat ed protein kinases, phosphatidylinositol 3-kinase, focal adhesion kinase, a nd protein kinase C. This paper will summarize the experimental evidence th at implicates these pathways in stellate cell activation, focusing on the e ffects of exposure to platelet-derived growth factor, tumor necrosis factor -alpha, and fibronectin. Implications for alcohol-induced hepatic fibrosis and future directions for research will also be discussed.