Vascular endothelial growth factor promotes the activation of hepatic stellate cells in chronic schistosomiasis

Jie Luo, Yuejin Liang, Fanping Kong, Jingfan Qiu, Xinjian Liu, Ailing Chen, Bruce Luxon, Hannah W. Wu, Yong Wang

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The activation of hepatic stellate cells (HSCs) is a key event in fibrotic pathogenesis. However, the mechanism involving activation of HSCs in chronic schistosomiasis is not entirely clear. Human HSC LX-2 and human umbilical vein endothelial cells (ECs) were cultured with Schistosoma japonicum antigens (SA) in vitro. Fibrosis-associated genes and cell proliferation were analyzed. HSCs were isolated from mice of chronic schistosomiasis with or without praziquantel (PZQ) treatment, followed by the microarray analysis for the liver fibrosis-associated pathways. Although SA inhibited the activation and proliferation of HSCs, it induced the EC proliferation and vascular endothelial growth factor-a (VEGF) production. VEGF significantly increased the proliferation of HSCs and upregulated the expression of collagen and α-smooth muscle actin. For in vivo study, we found that several fibrosis-associated pathways were involved in the HSCs during the reversal of liver fibrosis caused by schistosomiasis, including VEGF, platelet-derived growth factor, tumor necrosis factor and endothelin-1 pathways. The Ingenuity Pathway Analysis showed that VEGF directly regulated several pro-fibrotic and immune cytokine genes in HSCs, including integrin, fibronectin, interferon-γ, interleukin (IL)-6 and IL-10. Our data indicated the critical role of VEGF signaling in HSC activation in chronic schistosomiasis and highlighted several promising genes and pathways in HSCs as potential targets for therapeutic treatment of liver fibrosis.

Original languageEnglish (US)
Pages (from-to)399-407
Number of pages9
JournalImmunology and Cell Biology
Volume95
Issue number4
DOIs
StatePublished - Apr 1 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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