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Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell activation and fibrogenesis

Anthony, BJ, Mathieson, W, de Castro-Borges, W and Allen, JT 2010, 'Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell activation and fibrogenesis' , Experimental parasitology, 124 (4) , pp. 409-420.

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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 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.

    Item Type: Article
    Themes: Health and Wellbeing
    Schools: Colleges and Schools > College of Science & Technology > School of Environment and Life Sciences > Ecosystems and Environment Research Centre
    Journal or Publication Title: Experimental parasitology
    Publisher: Elsevier
    Refereed: Yes
    ISSN: 1090-2449
    Depositing User: JT Allen
    Date Deposited: 06 Oct 2011 10:20
    Last Modified: 20 Aug 2013 18:11
    URI: http://usir.salford.ac.uk/id/eprint/17907

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