Universidad Peruana Cayetano Heredia

Mechanisms of liver fibrosis associated with experimental fasciola hepatica infection: Roles of Fas2 proteinase and hepatic stellate cell activation

Mechanisms of liver fibrosis associated with experimental fasciola hepatica infection: Roles of Fas2 proteinase and hepatic stellate cell activation

Marcos, L.A.; Terashima, A.; Yi, P.; Andrade, R.; Cubero, F.J.; Albanis, E.; Gotuzzo Herencia, José Eduardo; Espinoza, J.R.; Friedman, S.L.
URI: https://hdl.handle.net/20.500.12866/11191
Fecha: 2011

Resumen:

We have evaluated the possible mechanisms of liver fibrosis caused by Fasciola hepatica in an animal model and in culture using immortalized human stellate cells. Liver biopsies of F. hepatica-infected rats were performed at wk 8 and 16. Serum-starved LX-2 cells, a human stellate cell line, were exposed to increasing concentrations of Fas2 antigen. The expression of key fibrosis-related genes was evaluated by qRT-PCR. There was a significant correlation between fibrogenic gene expression and both intensity and duration of infection. LX-2 cells exposed to Fas2 showed progressively increased expression of mRNAs for Collagen I, alpha-smooth muscle-actin, platelet-derived growth factor beta receptor, and tissue inhibitor of metalloproteinase II; inhibition of Fas2 cysteine proteinase activity by E-64 abrogated these increases, suggesting that the protease activity of Fas2 is involved in fibrogenic stimulation. In summary, F. hepatica infection is associated with up-regulation of mRNAs associated with hepatic fibrogenesis in vivo and in activated hepatic stellate cells.

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