Treatment of experimental hepatic fibrosis by combinational delivery of urokinase-type plasminogen activator and hepatocyte growth factor genes

Autor: Hui Qiang, Ze-Guang Han, Wei-Fen Xie, Yong Lin, Xiu-Jiang Yang, Xin Zeng, Wei-Zhong Chen, Zhong-Bing Zhang, Yue-Xiang Chen, Xin Zhang
Rok vydání: 2005
Předmět:
Zdroj: Liver international : official journal of the International Association for the Study of the Liver. 25(4)
ISSN: 1478-3223
Popis: Purpose: To investigate the effect of combinational delivery of urokinase-type plasminogen activator (uPA) and hepatocyte growth factor (HGF) genes on hepatic fibrosis. Methods: Replication-deficient adenoviral vectors expressing either human HGF (AdHGF) or uPA (AduPA) were generated. HGF gene was transferred into primary cultured hepatocytes and uPA gene to hepatic stellate cell (HSC) to investigate the effect on the biological character of cells. Combinational adenoviruses were infused into hepatic fibrosis rats. Serum markers as well as histological and immunohistochemical examination were carried out to test the reversal of hepatic fibrosis. Results: Transfection of exogenous HGF gene induced expression of c-met/HGF receptor and stimulated hepatocyte proliferation. uPA gene delivered into HSC decreased the amount of collagen types I and III accompanied with the increased expression of matrix metalloproteinase-2. In vivo, the area of extracellular matrix in the fibrotic liver decreased to 72% in AdHGF-treated rats (P
Databáze: OpenAIRE