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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doaj-bf8900e7fadd49bea188a004f19211b52020-11-24T20:57:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-11-01910.3389/fgene.2018.00556427704FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory SignalingXiaohua Tan0Xiaohua Tan1Hongmei Zhu2Qianyu Tao3Lisha Guo4Tianfang Jiang5Le Xu6Ruo Yang7Xiayu Wei8Jin Wu9Xiaokun Li10Xiaokun Li11Jin-San Zhang12Jin-San Zhang13Jin-San Zhang14School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaQingdao University Medical College, Qingdao, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Life Sciences, Wenzhou University, Wenzhou, ChinaInstitute of Life Sciences, Wenzhou University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaInstitute of Life Sciences, Wenzhou University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaThe First Affiliated Hospital, Wenzhou Medical University, Wenzhou, ChinaInstitute of Life Sciences, Wenzhou University, Wenzhou, ChinaIschemia-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.https://www.frontiersin.org/article/10.3389/fgene.2018.00556/fullFGF10ischemia-reperfusionacute kidney injuryautophagyinflammationHMGB1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaohua Tan Xiaohua Tan Hongmei Zhu Qianyu Tao Lisha Guo Tianfang Jiang Le Xu Ruo Yang Xiayu Wei Jin Wu Xiaokun Li Xiaokun Li Jin-San Zhang Jin-San Zhang Jin-San Zhang |
spellingShingle |
Xiaohua Tan Xiaohua Tan Hongmei Zhu Qianyu Tao Lisha Guo Tianfang Jiang Le Xu Ruo Yang Xiayu Wei Jin Wu Xiaokun Li Xiaokun Li Jin-San Zhang Jin-San Zhang Jin-San Zhang FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling Frontiers in Genetics FGF10 ischemia-reperfusion acute kidney injury autophagy inflammation HMGB1 |
author_facet |
Xiaohua Tan Xiaohua Tan Hongmei Zhu Qianyu Tao Lisha Guo Tianfang Jiang Le Xu Ruo Yang Xiayu Wei Jin Wu Xiaokun Li Xiaokun Li Jin-San Zhang Jin-San Zhang Jin-San Zhang |
author_sort |
Xiaohua Tan |
title |
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_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_sort |
fgf10 protects against renal ischemia/reperfusion injury by regulating autophagy and inflammatory signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2018-11-01 |
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. |
topic |
FGF10 ischemia-reperfusion acute kidney injury autophagy inflammation HMGB1 |
url |
https://www.frontiersin.org/article/10.3389/fgene.2018.00556/full |
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