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

Anthony, BJ; Mathieson, W; de Castro-Borges, W; Allen, JT

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.

Citation

Anthony, B., Mathieson, W., de Castro-Borges, W., & Allen, J. (2010). Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell activation and fibrogenesis. Experimental Parasitology, 124(4), 409-420. https://doi.org/10.1016/j.exppara.2009.12.009

• Journal Article Type: Article
• Publication Date: Jan 1, 2010
• Deposit Date: Oct 6, 2011
• Journal: Experimental parasitology
• Print ISSN: 0014-4894
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 124
• Issue: 4
• Pages: 409-420
• DOI: https://doi.org/10.1016/j.exppara.2009.12.009
• Publisher URL: http://dx.doi.org/10.1016/j.exppara.2009.12.009