MECHANISMS OF LIVER FIBROSIS ASSOCIATED WITH EXPERIMENTAL FASCIOLA HEPATICA INFECTION: ROLES OF FAS2 PROTEINASE AND HEPATIC STELLATE CELL ACTIVATION

作者：Marcos Luis A^*; Terashima Angelica; Yi Pedro; Andrade Roy; Cubero Francisco J; Albanis Efsevia; Gotuzzo Eduardo; Espinoza Jose R; Friedman Scott L

来源：The Journal of Parasitology, 2011, 97(1): 82-87.

DOI：10.1645/GE-2420.1

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 11; 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.

• 出版日期2011-2