title: Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell activation and fibrogenesis.
abstract: Eggs of Schistosoma mansoni trapped in human liver can lead to fibrosis. Since liver fibrosis requires activation of hepatic stellate cells (HSC) from a quiescent to a myofibroblastic phenotype, we investigated the effects of S. mansoni eggs on this process using in vitro co-cultures with human HSC and evaluated established biomarkers for activation and fibrosis. HSC demonstrate significantly reduced expression of alpha-smooth muscle actin (p<0.001), connective tissue growth factor (p<0.01) and type I collagen (p<0.001) but significantly increased expression of peroxisome proliferator-activated receptor-gamma (p<0.01). Morphologically, HSC exhibited elongated fine cellular processes and reduced size, increased accumulation of lipid droplets and reduced expression and organization of alpha-smooth muscle actin and F-actin stress fibres. Additionally, schistosome eggs prevented the HSC fibrogenic response to exogenous transforming growth factor-beta. In summary, schistosome eggs blocked fibrogenesis in HSC, a finding which may have implications for our understanding of the fibrotic pathology in S. mansoni infections.
authors.affiliation: Centre for Parasitology and Disease, Biomedical Sciences Research Institute, University of Salford, Manchester M5 4WT, UK.
authors.forename: Barrie
authors.initials: B
authors.lastname: Anthony
authors.forename: William
authors.initials: W
authors.lastname: Mathieson
authors.forename: William
authors.initials: W
authors.lastname: de Castro-Borges
authors.forename: Jeremy
authors.initials: J
authors.lastname: Allen
mesh_terms: D000818:Animals; D002460:Cell Line; D019084:Fluorescent Antibody Technique, Indirect; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000187:drug effects / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D008099:Liver / Q000166:cytology / Q000469:parasitology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000469:parasitology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008858:Microscopy, Phase-Contrast; D047495:PPAR gamma / Q000096:biosynthesis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D047495:PPAR gamma; D016212:Transforming Growth Factor beta