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Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway

Kidney is one of the most vulnerable organs in sepsis, resulting in sepsis-associated acute kidney injury (SA-AKI), which brings about not only morbidity but also mortality of sepsis. Ferroptosis is a new kind of death type of cells elicited by iron-dependent lipid peroxidation, which participates i...

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Autores principales: Qiongyue, Zhang, Xin, Yang, Meng, Peng, Sulin, Mi, Yanlin, Wang, Xinyi, Li, Xuemin, Song
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970707/
https://www.ncbi.nlm.nih.gov/pubmed/35370723
http://dx.doi.org/10.3389/fphar.2022.857067
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author Qiongyue, Zhang
Xin, Yang
Meng, Peng
Sulin, Mi
Yanlin, Wang
Xinyi, Li
Xuemin, Song
author_facet Qiongyue, Zhang
Xin, Yang
Meng, Peng
Sulin, Mi
Yanlin, Wang
Xinyi, Li
Xuemin, Song
author_sort Qiongyue, Zhang
collection PubMed
description Kidney is one of the most vulnerable organs in sepsis, resulting in sepsis-associated acute kidney injury (SA-AKI), which brings about not only morbidity but also mortality of sepsis. Ferroptosis is a new kind of death type of cells elicited by iron-dependent lipid peroxidation, which participates in pathogenesis of sepsis. The aim of this study was to verify the occurrence of ferroptosis in the SA-AKI pathogenesis and demonstrate that post-treatment with irisin could restrain ferroptosis and alleviate SA-AKI via activating the SIRT1/Nrf2 signaling pathway. We established a SA-AKI model by cecal ligation and puncture (CLP) operation and an in vitro model in LPS-induced HK2 cells, respectively. Our result exhibited that irisin inhibited the level of ferroptosis and ameliorated kidney injury in CLP mice, as evidenced by reducing the ROS production, iron content, and MDA level and increasing the GSH level, as well as the alteration of ferroptosis-related protein (GPX4 and ACSL4) expressions in renal, which was consistent with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Additionally, we consistently observed that irisin inhibited ROS accumulation, iron production, and ameliorated mitochondrial dysfunction in LPS-stimulated HK-2 cells. Furthermore, our result also revealed that irisin could activate SIRT1/Nrf2 signaling pathways both in vivo and vitro. However, the beneficial effects of irisin were weakened by EX527 (an inhibitor of SIRT1) in vivo and by SIRT1 siRNA in vitro. In conclusion, irisin could protect against SA-AKI through ferroptotic resistance via activating the SIRT1/Nrf2 signaling pathway.
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spelling pubmed-89707072022-04-01 Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway Qiongyue, Zhang Xin, Yang Meng, Peng Sulin, Mi Yanlin, Wang Xinyi, Li Xuemin, Song Front Pharmacol Pharmacology Kidney is one of the most vulnerable organs in sepsis, resulting in sepsis-associated acute kidney injury (SA-AKI), which brings about not only morbidity but also mortality of sepsis. Ferroptosis is a new kind of death type of cells elicited by iron-dependent lipid peroxidation, which participates in pathogenesis of sepsis. The aim of this study was to verify the occurrence of ferroptosis in the SA-AKI pathogenesis and demonstrate that post-treatment with irisin could restrain ferroptosis and alleviate SA-AKI via activating the SIRT1/Nrf2 signaling pathway. We established a SA-AKI model by cecal ligation and puncture (CLP) operation and an in vitro model in LPS-induced HK2 cells, respectively. Our result exhibited that irisin inhibited the level of ferroptosis and ameliorated kidney injury in CLP mice, as evidenced by reducing the ROS production, iron content, and MDA level and increasing the GSH level, as well as the alteration of ferroptosis-related protein (GPX4 and ACSL4) expressions in renal, which was consistent with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Additionally, we consistently observed that irisin inhibited ROS accumulation, iron production, and ameliorated mitochondrial dysfunction in LPS-stimulated HK-2 cells. Furthermore, our result also revealed that irisin could activate SIRT1/Nrf2 signaling pathways both in vivo and vitro. However, the beneficial effects of irisin were weakened by EX527 (an inhibitor of SIRT1) in vivo and by SIRT1 siRNA in vitro. In conclusion, irisin could protect against SA-AKI through ferroptotic resistance via activating the SIRT1/Nrf2 signaling pathway. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8970707/ /pubmed/35370723 http://dx.doi.org/10.3389/fphar.2022.857067 Text en Copyright © 2022 Qiongyue, Xin, Meng, Sulin, Yanlin, Xinyi and Xuemin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Qiongyue, Zhang
Xin, Yang
Meng, Peng
Sulin, Mi
Yanlin, Wang
Xinyi, Li
Xuemin, Song
Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway
title Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway
title_full Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway
title_fullStr Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway
title_full_unstemmed Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway
title_short Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway
title_sort post-treatment with irisin attenuates acute kidney injury in sepsis mice through anti-ferroptosis via the sirt1/nrf2 pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970707/
https://www.ncbi.nlm.nih.gov/pubmed/35370723
http://dx.doi.org/10.3389/fphar.2022.857067
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