Schistosoma mansoni: Egg-induced downregulation of hepatic stellate cell activation and fibrogenesis |
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Authors: | Barrie Anthony William de Castro-Borges Jeremy Allen |
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Affiliation: | a Centre for Parasitology and Disease, Biomedical Sciences Research Institute, University of Salford, Manchester M5 4WT, UK b Department of Biology, University of York, PO Box 373, York YO10 5W, UK |
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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 α-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-γ (p < 0.01). Morphologically, HSC exhibited elongated fine cellular processes and reduced size, increased accumulation of lipid droplets and reduced expression and organization of α-smooth muscle actin and F-actin stress fibres. Additionally, schistosome eggs prevented the HSC fibrogenic response to exogenous transforming growth factor-β. 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. |
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Keywords: | Schistosomes Liver fibrosis Relative gene expression Immunocytochemistry Trematodes |
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