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Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression

BACKGROUND: The 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 vit...

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Autores principales: Wang, Jianxin, Xu, Feifan, Zhu, Dandan, Duan, Yinong, Chen, Jinling, Sun, Xiaolei, He, Xue, Li, Pan, Sun, Wei, Feng, Jinrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140669/
https://www.ncbi.nlm.nih.gov/pubmed/25144704
http://dx.doi.org/10.1371/journal.pntd.0003106
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author Wang, Jianxin
Xu, Feifan
Zhu, Dandan
Duan, Yinong
Chen, Jinling
Sun, Xiaolei
He, Xue
Li, Pan
Sun, Wei
Feng, Jinrong
author_facet Wang, Jianxin
Xu, Feifan
Zhu, Dandan
Duan, Yinong
Chen, Jinling
Sun, Xiaolei
He, Xue
Li, Pan
Sun, Wei
Feng, Jinrong
author_sort Wang, Jianxin
collection PubMed
description BACKGROUND: The 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 FINDINGS: In 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, 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 GW501516. CONCLUSIONS/SIGNIFICANCE: Our data suggest that SEA can induce HSC apoptosis by downregulating Akt expression and upregulating p53-dependent DR5 expression.
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spelling pubmed-41406692014-08-25 Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression Wang, Jianxin Xu, Feifan Zhu, Dandan Duan, Yinong Chen, Jinling Sun, Xiaolei He, Xue Li, Pan Sun, Wei Feng, Jinrong PLoS Negl Trop Dis Research Article BACKGROUND: The 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 FINDINGS: In 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, 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 GW501516. CONCLUSIONS/SIGNIFICANCE: Our data suggest that SEA can induce HSC apoptosis by downregulating Akt expression and upregulating p53-dependent DR5 expression. Public Library of Science 2014-08-21 /pmc/articles/PMC4140669/ /pubmed/25144704 http://dx.doi.org/10.1371/journal.pntd.0003106 Text en © 2014 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Jianxin
Xu, Feifan
Zhu, Dandan
Duan, Yinong
Chen, Jinling
Sun, Xiaolei
He, Xue
Li, Pan
Sun, Wei
Feng, Jinrong
Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression
title Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression
title_full Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression
title_fullStr Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression
title_full_unstemmed Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression
title_short Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression
title_sort schistosoma japonicum soluble egg antigens facilitate hepatic stellate cell apoptosis by downregulating akt expression and upregulating p53 and dr5 expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140669/
https://www.ncbi.nlm.nih.gov/pubmed/25144704
http://dx.doi.org/10.1371/journal.pntd.0003106
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