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However, the mechanism involving activation of HSCs in chronic schistosomiasis is not entirely clear. Human HSC LX\u20102 and human umbilical vein endothelial cells (ECs) were cultured with <jats:italic>Schistosoma japonicum<\/jats:italic> antigens (SA) <jats:italic>in vitro<\/jats:italic>. Fibrosis\u2010associated 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\u2010associated pathways. Although SA inhibited the activation and proliferation of HSCs, it induced the EC proliferation and vascular endothelial growth factor\u2010a (VEGF) production. VEGF significantly increased the proliferation of HSCs and upregulated the expression of collagen and \u03b1\u2010smooth muscle actin. For <jats:italic>in vivo<\/jats:italic> study, we found that several fibrosis\u2010associated pathways were involved in the HSCs during the reversal of liver fibrosis caused by schistosomiasis, including VEGF, platelet\u2010derived growth factor, tumor necrosis factor and endothelin\u20101 pathways. The Ingenuity Pathway Analysis showed that VEGF directly regulated several pro\u2010fibrotic and immune cytokine genes in HSCs, including integrin, fibronectin, interferon\u2010\u03b3, interleukin (IL)\u20106 and IL\u201010. 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.<\/jats:p>","DOI":"10.1038\/icb.2016.109","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T09:20:55Z","timestamp":1478164855000},"page":"399-407","source":"Crossref","is-referenced-by-count":34,"title":["Vascular endothelial growth factor promotes the activation of hepatic stellate cells in chronic schistosomiasis"],"prefix":"10.1111","volume":"95","author":[{"given":"Jie","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University  Nanjing China"},{"name":"Comprehensive Laboratory, Ningbo International Travel Healthcare Center  Ningbo 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