title: Mechanisms of liver fibrosis associated with experimental Fasciola hepatica infection: roles of Fas2 proteinase and hepatic stellate cell activation.
abstract: 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.
authors.affiliation: Washington University School of Medicine, Infectious Diseases Division, St Louis, Missouri, USA. lmarcos@dom.wustl.edu
authors.forename: Luis A
authors.initials: LA
authors.lastname: Marcos
authors.forename: Angélica
authors.initials: A
authors.lastname: Terashima
authors.forename: Pedro
authors.initials: P
authors.lastname: Yi
authors.forename: Roy
authors.initials: R
authors.lastname: Andrade
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Cubero
authors.forename: Efsevia
authors.initials: E
authors.lastname: Albanis
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gotuzzo
authors.forename: Jose R
authors.initials: JR
authors.lastname: Espinoza
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
mesh_terms: D000199:Actins / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D002460:Cell Line; D003094:Collagen / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004195:Disease Models, Animal; D005210:Fasciola hepatica / Q000201:enzymology* / Q000472:pathogenicity; D005211:Fascioliasis / Q000150:complications* / Q000473:pathology; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000473:pathology; D008297:Male; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics
chemical_list: D000199:Actins; D000947:Antigens, Helminth; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D020797:Receptor, Platelet-Derived Growth Factor beta; D003546:Cysteine Endopeptidases; C507847:Fas2 antigen, Fasciola hepatica