The Role Of The Plasminogen Activator Inhibitor-1 In The Pathogenesis Of Hepatic Fibrosis

[Background and Objective]Hepatic fibrosis, characterized by the overproduction and accumulation of hepatic extracellular matrix (ECM), was the common and important pathological changes in the chronic liver diseases, through which the chronic hepatitis developed into cirrhosis. Hepatic stellate cells (HSC), located at Disse's space in liver, were widely recognized as the main resource of hepatic ECM and the cellular basis for hepatic fibrosis.Recently, many reports have shown that the fibrinolytic system, especially urokinasetype plasminogen activator (uPA) and its main inhibitor-plasminogen activator inhibitor-1 (PAI-1), was involved in the fibrogenesis of liver. PAI-1 can lead to excessive ECM synthesis and secretion through preventing uPA activating plasminogen and degrading matrix metalloproteinases (MMPs) activation.PAI-1 is a single strand glucoprotein with molecular weight 52kD. Among its 379 amino-acid residues, a signal peptide composed by 23 amino-acid residues is related closely to occurrence of many chronic diseases and phymatosis since it exerts an effect on regulating genetic transcription, cell cycle and maintaining cell survival in many kinds of corpuscular physiological and pathological procedures. So far, there are still no reports on relationship between PAI-1 and collagen types I and III in hepatic fibrosis.In recent years, much of the attention in gene therapy has focused on RNA interference (RNAi), a promising therapeutic technique aiming to switch off targeted genes. Studies showed that RNAi is a powerful tool to silence disease-causing gene...