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FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling

Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is com...

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Autores principales: Tan, Xiaohua, Zhu, Hongmei, Tao, Qianyu, Guo, Lisha, Jiang, Tianfang, Xu, Le, Yang, Ruo, Wei, Xiayu, Wu, Jin, Li, Xiaokun, Zhang, Jin-San
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265307/
https://www.ncbi.nlm.nih.gov/pubmed/30532765
http://dx.doi.org/10.3389/fgene.2018.00556
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author Tan, Xiaohua
Zhu, Hongmei
Tao, Qianyu
Guo, Lisha
Jiang, Tianfang
Xu, Le
Yang, Ruo
Wei, Xiayu
Wu, Jin
Li, Xiaokun
Zhang, Jin-San
author_facet Tan, Xiaohua
Zhu, Hongmei
Tao, Qianyu
Guo, Lisha
Jiang, Tianfang
Xu, Le
Yang, Ruo
Wei, Xiayu
Wu, Jin
Li, Xiaokun
Zhang, Jin-San
author_sort Tan, Xiaohua
collection PubMed
description Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is complex and controversial. Fibroblast growth factor 10 (FGF10), a multifunctional FGF family member, was reported to exert protective effect against cerebral ischemia injury and myocardial damage. Whether FGF10 has similar beneficial effect, and if so whether autophagy is associated with the potential protective activity against AKI has not been investigated. Herein, we report that FGF10 treatment improved renal function and histological integrity in a rat model of renal I/R injury. We observed that FGF10 efficiently reduced I/R-induced elevation in blood urea nitrogen, serum creatinine as well as apoptosis induction of RTCs. Interestingly, autophagy activation following I/R was suppressed by FGF10 treatment based on the immunohistochemistry staining and immunoblot analyses of LC3, Beclin-1 and SQSTM1/p62. Moreover, combined treatment of FGF10 with Rapamycin partially reversed the renoprotective effect of FGF10 suggesting the involvement of mTOR pathway in the process. Interestingly, FGF10 also inhibited the release of HMGB1 from the nucleus to the extracellular domain and regulated the expression of inflammatory cytokines such as TNF-α, IL-1β and IL-6. Together, these results indicate that FGF10 could alleviate kidney I/R injury by suppressing excessive autophagy and inhibiting inflammatory response and may therefore have the potential to be used for the prevention and perhaps treatment of I/R-associated AKI.
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spelling pubmed-62653072018-12-07 FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling Tan, Xiaohua Zhu, Hongmei Tao, Qianyu Guo, Lisha Jiang, Tianfang Xu, Le Yang, Ruo Wei, Xiayu Wu, Jin Li, Xiaokun Zhang, Jin-San Front Genet Genetics Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is complex and controversial. Fibroblast growth factor 10 (FGF10), a multifunctional FGF family member, was reported to exert protective effect against cerebral ischemia injury and myocardial damage. Whether FGF10 has similar beneficial effect, and if so whether autophagy is associated with the potential protective activity against AKI has not been investigated. Herein, we report that FGF10 treatment improved renal function and histological integrity in a rat model of renal I/R injury. We observed that FGF10 efficiently reduced I/R-induced elevation in blood urea nitrogen, serum creatinine as well as apoptosis induction of RTCs. Interestingly, autophagy activation following I/R was suppressed by FGF10 treatment based on the immunohistochemistry staining and immunoblot analyses of LC3, Beclin-1 and SQSTM1/p62. Moreover, combined treatment of FGF10 with Rapamycin partially reversed the renoprotective effect of FGF10 suggesting the involvement of mTOR pathway in the process. Interestingly, FGF10 also inhibited the release of HMGB1 from the nucleus to the extracellular domain and regulated the expression of inflammatory cytokines such as TNF-α, IL-1β and IL-6. Together, these results indicate that FGF10 could alleviate kidney I/R injury by suppressing excessive autophagy and inhibiting inflammatory response and may therefore have the potential to be used for the prevention and perhaps treatment of I/R-associated AKI. Frontiers Media S.A. 2018-11-23 /pmc/articles/PMC6265307/ /pubmed/30532765 http://dx.doi.org/10.3389/fgene.2018.00556 Text en Copyright © 2018 Tan, Zhu, Tao, Guo, Jiang, Xu, Yang, Wei, Wu, Li and Zhang. 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 Genetics
Tan, Xiaohua
Zhu, Hongmei
Tao, Qianyu
Guo, Lisha
Jiang, Tianfang
Xu, Le
Yang, Ruo
Wei, Xiayu
Wu, Jin
Li, Xiaokun
Zhang, Jin-San
FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling
title FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling
title_full FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling
title_fullStr FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling
title_full_unstemmed FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling
title_short FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling
title_sort fgf10 protects against renal ischemia/reperfusion injury by regulating autophagy and inflammatory signaling
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265307/
https://www.ncbi.nlm.nih.gov/pubmed/30532765
http://dx.doi.org/10.3389/fgene.2018.00556
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