Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression |
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Authors: | Jianxin Wang Feifan Xu Dandan Zhu Yinong Duan Jinling Chen Xiaolei Sun Xue He Pan Li Wei Sun Jinrong Feng |
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Institution: | 1. Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People''s Republic of China.; 2. Department of Pathogen Biology, School of Medicine, Nantong University, Nantong, Jiangsu, People''s Republic of China.; Monash University, Australia, |
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Abstract: | BackgroundThe induction of hepatic stellate cell (HSC) apoptosis has potential as a potent strategy to diminish the progression of liver fibrosis. Previous studies have demonstrated the ability of soluble egg antigens (SEA) from schistosomes to inhibit HSC activation and to induce apoptosis in vitro. In this study, we aimed to explore the mechanism of SEA-induced apoptosis in HSCs.Methodology/Principal FindingsIn this study, we found that SEA could upregulate p53 and DR5 and downregulate the p-Akt. The apoptosis of HSCs induced by SEA could be reduced in HSCs that were treated with p53-specific siRNA and in HSCs that were treated with DR5-specific shRNA. In addition, {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516, which enhances the expression of Akt, could also decrease the SEA-induced HSC apoptosis. We also found that the increased expression of p53 and DR5 induced by SEA through Mdm2 were reduced by {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516.Conclusions/SignificanceOur data suggest that SEA can induce HSC apoptosis by downregulating Akt expression and upregulating p53-dependent DR5 expression. |
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