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FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway
Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemothera...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532427/ https://www.ncbi.nlm.nih.gov/pubmed/37762517 http://dx.doi.org/10.3390/ijms241814215 |
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author | Wang, Lihui Cheng, Feiyan Pan, Rumeng Cui, Zhiwei She, Jing Zhang, Yidan Yang, Xinyuan |
author_facet | Wang, Lihui Cheng, Feiyan Pan, Rumeng Cui, Zhiwei She, Jing Zhang, Yidan Yang, Xinyuan |
author_sort | Wang, Lihui |
collection | PubMed |
description | Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemotherapeutic agents plays an important role in the development of POF. However, the exact effects of nuclear factor-erythroid 2-related factor2 (NRF2), a pivotal anti-oxidative factor, are still unknown in chemotherapy-associated POF. Firstly, we manipulated NRF2 expressions on a genetic or pharmaceutical level in cisplatin-injured granulosa cell models. The results indicate that the increasing NRF2 in cisplatin-injured cells was just compensatory and not enough to resist the accumulated stress. Upregulation of NRF2 could protect granulosa cells against cisplatin via elevating autophagic level by using an autophagic activator (rapamycin) and inhibitor (chloroquine). Additionally, exogenous FGF2 exerted a protective role by increasing NRF2 expression and promoting its nuclear translocation. Meanwhile, the results in cisplatin-POF mice models were consistent with what was found in injured cells. In conclusion, our research proved that FGF2 rescued cisplatin-injured granulosa cells through the NRF2-autophagy pathway and might provide a possible alternative treatment choice by targeting NRF2 for POF patients who are intolerant or unsuitable to FGF2. |
format | Online Article Text |
id | pubmed-10532427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105324272023-09-28 FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway Wang, Lihui Cheng, Feiyan Pan, Rumeng Cui, Zhiwei She, Jing Zhang, Yidan Yang, Xinyuan Int J Mol Sci Article Premature ovarian failure (POF) is a complicated disorder related to the apoptosis of granulosa cells. The incidence of chemotherapy-associated POF is rising dramatically owing to the increasing proportion of cancer in adolescents. According to previous studies, oxidative stress caused by chemotherapeutic agents plays an important role in the development of POF. However, the exact effects of nuclear factor-erythroid 2-related factor2 (NRF2), a pivotal anti-oxidative factor, are still unknown in chemotherapy-associated POF. Firstly, we manipulated NRF2 expressions on a genetic or pharmaceutical level in cisplatin-injured granulosa cell models. The results indicate that the increasing NRF2 in cisplatin-injured cells was just compensatory and not enough to resist the accumulated stress. Upregulation of NRF2 could protect granulosa cells against cisplatin via elevating autophagic level by using an autophagic activator (rapamycin) and inhibitor (chloroquine). Additionally, exogenous FGF2 exerted a protective role by increasing NRF2 expression and promoting its nuclear translocation. Meanwhile, the results in cisplatin-POF mice models were consistent with what was found in injured cells. In conclusion, our research proved that FGF2 rescued cisplatin-injured granulosa cells through the NRF2-autophagy pathway and might provide a possible alternative treatment choice by targeting NRF2 for POF patients who are intolerant or unsuitable to FGF2. MDPI 2023-09-18 /pmc/articles/PMC10532427/ /pubmed/37762517 http://dx.doi.org/10.3390/ijms241814215 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Lihui Cheng, Feiyan Pan, Rumeng Cui, Zhiwei She, Jing Zhang, Yidan Yang, Xinyuan FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway |
title | FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway |
title_full | FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway |
title_fullStr | FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway |
title_full_unstemmed | FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway |
title_short | FGF2 Rescued Cisplatin-Injured Granulosa Cells through the NRF2-Autophagy Pathway |
title_sort | fgf2 rescued cisplatin-injured granulosa cells through the nrf2-autophagy pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532427/ https://www.ncbi.nlm.nih.gov/pubmed/37762517 http://dx.doi.org/10.3390/ijms241814215 |
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