Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress

Chronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeut...

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Autores principales: Li, Xiaosong, Pan, E., Zhu, Junke, Xu, Lei, Chen, Xuemei, Li, Jingjing, Liang, Li, Hu, Yuan, Xia, Jie, Chen, Juan, Chen, Wannan, Hu, Jieli, Wang, Kai, Tang, Ni, Huang, Ailong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823916/
https://www.ncbi.nlm.nih.gov/pubmed/29472690
http://dx.doi.org/10.1038/s41598-018-21847-3
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author Li, Xiaosong
Pan, E.
Zhu, Junke
Xu, Lei
Chen, Xuemei
Li, Jingjing
Liang, Li
Hu, Yuan
Xia, Jie
Chen, Juan
Chen, Wannan
Hu, Jieli
Wang, Kai
Tang, Ni
Huang, Ailong
author_facet Li, Xiaosong
Pan, E.
Zhu, Junke
Xu, Lei
Chen, Xuemei
Li, Jingjing
Liang, Li
Hu, Yuan
Xia, Jie
Chen, Juan
Chen, Wannan
Hu, Jieli
Wang, Kai
Tang, Ni
Huang, Ailong
author_sort Li, Xiaosong
collection PubMed
description Chronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeutic agent-related HBV reactivation remain unclear. Here, we report that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) plays a central role in cisplatin-induced HBV transcription and replication. First, cisplatin treatment upregulated the expression levels of PGC-1α and hepatocyte nuclear factor 4 alpha (HNF-4α) in both HBV-replicating cells and an HBV-transgenic mouse model. PGC-1α coactivates with HNF-4α, which interacts with a core promoter and enhancer II region of HBV genome, thereby promoting HBV production. In contrast, knockdown of PGC-1α and HNF-4α by RNA interference in hepatoma cells reversed HBV activation in response to cisplatin. Additionally, PGC-1α upregulation depended on cisplatin-mediated endoplasmic reticulum (ER) stress. We further observed that the recruitment of cyclic AMP-responsive element-binding protein plays a crucial role for PGC-1α transcriptional activation in cisplatin-treated cells. Finally, pharmacologic inhibition of ER stress impaired PGC-1α upregulation and HBV production induced by cisplatin treatment. These findings demonstrate novel molecular mechanisms indicating that ER stress-PGC1α signaling pathway plays a critical role in cisplatin-evoked HBV reactivation.
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spelling pubmed-58239162018-02-26 Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress Li, Xiaosong Pan, E. Zhu, Junke Xu, Lei Chen, Xuemei Li, Jingjing Liang, Li Hu, Yuan Xia, Jie Chen, Juan Chen, Wannan Hu, Jieli Wang, Kai Tang, Ni Huang, Ailong Sci Rep Article Chronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeutic agent-related HBV reactivation remain unclear. Here, we report that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) plays a central role in cisplatin-induced HBV transcription and replication. First, cisplatin treatment upregulated the expression levels of PGC-1α and hepatocyte nuclear factor 4 alpha (HNF-4α) in both HBV-replicating cells and an HBV-transgenic mouse model. PGC-1α coactivates with HNF-4α, which interacts with a core promoter and enhancer II region of HBV genome, thereby promoting HBV production. In contrast, knockdown of PGC-1α and HNF-4α by RNA interference in hepatoma cells reversed HBV activation in response to cisplatin. Additionally, PGC-1α upregulation depended on cisplatin-mediated endoplasmic reticulum (ER) stress. We further observed that the recruitment of cyclic AMP-responsive element-binding protein plays a crucial role for PGC-1α transcriptional activation in cisplatin-treated cells. Finally, pharmacologic inhibition of ER stress impaired PGC-1α upregulation and HBV production induced by cisplatin treatment. These findings demonstrate novel molecular mechanisms indicating that ER stress-PGC1α signaling pathway plays a critical role in cisplatin-evoked HBV reactivation. Nature Publishing Group UK 2018-02-22 /pmc/articles/PMC5823916/ /pubmed/29472690 http://dx.doi.org/10.1038/s41598-018-21847-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Xiaosong
Pan, E.
Zhu, Junke
Xu, Lei
Chen, Xuemei
Li, Jingjing
Liang, Li
Hu, Yuan
Xia, Jie
Chen, Juan
Chen, Wannan
Hu, Jieli
Wang, Kai
Tang, Ni
Huang, Ailong
Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
title Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
title_full Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
title_fullStr Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
title_full_unstemmed Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
title_short Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
title_sort cisplatin enhances hepatitis b virus replication and pgc-1α expression through endoplasmic reticulum stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823916/
https://www.ncbi.nlm.nih.gov/pubmed/29472690
http://dx.doi.org/10.1038/s41598-018-21847-3
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