General features of hepatic stellate cells undergoing apoptosis in cirrhotic rat liver

Liver fibrosis represents a significant worldwide health problem. It is a response of liver to repeated injury and it is characterized by breakdown of normal extracellular matrix (ECM) resembling basement membrane in composition and by accumulation of ECM containing fibrillar type I collagen. Although more than one potential source of ECM exist, the largest part of connective tissue components is synthesized by activated hepatic stellate cells (HSC). Hepatic stellate cells are located in the space of Disse between endothelial cells and parenchymal cells and their main function is the uptake and storage of vitamin A and other retinoids. Inducing or accelerating their apoptosis is a potential way of liver fibrosis treatment. Aim of our study was to find out how collagen gell influences HSC as the effect of ECM on HSC apoptosis has not been studied yet. We have used gel made of type I collagen, the main component of fibrotic liver ECM, to study how it affects spontaneous apoptosis of HSC isolated from carbon tetrachloride damaged liver and the apoptosis of normal HSC exposed to apoptosis inducing agents, gliotoxin, cycloheximide and cytochalasin D, in vitro. HSC were prepared by perfusion of rat normal and cirrhotic liver with pronase and collagenase solutions, followed by centrifugation of the cell..