Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell activation and fibrogenesis.
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.
Anthony
Barrie
B
Centre for Parasitology and Disease, Biomedical Sciences Research Institute, University of Salford, Manchester M5 4WT, UK.
Mathieson
William
W
de Castro-Borges
William
W
Allen
Jeremy
J
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
D047495:PPAR gamma; D016212:Transforming Growth Factor beta