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

Barrie Anthony, William Mathieson, William de Castro-Borges, Jeremy Allen*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)409-420
Number of pages12
JournalExperimental Parasitology
Volume124
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Keywords

  • Immunocytochemistry
  • Liver fibrosis
  • Relative gene expression
  • Schistosomes
  • Trematodes

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