Apoptosis and oncotic necrosis: profibrotic signalling mechanisms of cell death

摘要

Liver fibrosis forms part of most chronic liver disease processes including alcoholic and non-alcoholic steatohepatitis, viral and autoimmune hepatitis and obstructive cholestasis1. Key features of fibrogenesis include activation of stellate cells and the deposition of excess extracellular matrix, especially the fibril-forming collagens I and III, in the space of Disse. These events can lead to a significant impairment of liver function and portal hypertension, and can enhance susceptibility to sepsis. The fibrotic response is initiated and maintained by acute and chronic cell injury. The fibrotic process can be stopped and even reversed by removing the chronic insult, by inducing cell death of activated stellate cells and by promoting degradation of the excess extracellular matrix. Thus, controlling cell death and its profibrotic signalling events are critical therapeutic strategies to prevent or reverse fibrosis.