Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress
Abstract 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 chemo...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/c8d4578523d9427fa093a7caa3943871 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:c8d4578523d9427fa093a7caa3943871 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:c8d4578523d9427fa093a7caa39438712021-12-02T12:32:21ZCisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress10.1038/s41598-018-21847-32045-2322https://doaj.org/article/c8d4578523d9427fa093a7caa39438712018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21847-3https://doaj.org/toc/2045-2322Abstract 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.Xiaosong LiE. PanJunke ZhuLei XuXuemei ChenJingjing LiLi LiangYuan HuJie XiaJuan ChenWannan ChenJieli HuKai WangNi TangAilong HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Xiaosong Li E. Pan Junke Zhu Lei Xu Xuemei Chen Jingjing Li Li Liang Yuan Hu Jie Xia Juan Chen Wannan Chen Jieli Hu Kai Wang Ni Tang Ailong Huang Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress |
| description |
Abstract 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. |
| format |
article |
| author |
Xiaosong Li E. Pan Junke Zhu Lei Xu Xuemei Chen Jingjing Li Li Liang Yuan Hu Jie Xia Juan Chen Wannan Chen Jieli Hu Kai Wang Ni Tang Ailong Huang |
| author_facet |
Xiaosong Li E. Pan Junke Zhu Lei Xu Xuemei Chen Jingjing Li Li Liang Yuan Hu Jie Xia Juan Chen Wannan Chen Jieli Hu Kai Wang Ni Tang Ailong Huang |
| author_sort |
Xiaosong Li |
| title |
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_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_sort |
cisplatin enhances hepatitis b virus replication and pgc-1α expression through endoplasmic reticulum stress |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/c8d4578523d9427fa093a7caa3943871 |
| work_keys_str_mv |
AT xiaosongli cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT epan cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT junkezhu cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT leixu cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT xuemeichen cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT jingjingli cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT liliang cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT yuanhu cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT jiexia cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT juanchen cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT wannanchen cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT jielihu cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT kaiwang cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT nitang cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress AT ailonghuang cisplatinenhanceshepatitisbvirusreplicationandpgc1aexpressionthroughendoplasmicreticulumstress |
| _version_ |
1718394120386379776 |