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Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling

Ischaemia‐reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI‐induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective r...

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Autores principales: Tan, Xiao‐Hua, Zheng, Xiao‐Meng, Yu, Li‐Xia, He, Jian, Zhu, Hong‐Mei, Ge, Xiu‐Ping, Ren, Xiao‐Li, Ye, Fa‐Qing, Bellusci, Saverio, Xiao, Jian, Li, Xiao‐Kun, Zhang, Jin‐San
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661260/
https://www.ncbi.nlm.nih.gov/pubmed/28544332
http://dx.doi.org/10.1111/jcmm.13203
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author Tan, Xiao‐Hua
Zheng, Xiao‐Meng
Yu, Li‐Xia
He, Jian
Zhu, Hong‐Mei
Ge, Xiu‐Ping
Ren, Xiao‐Li
Ye, Fa‐Qing
Bellusci, Saverio
Xiao, Jian
Li, Xiao‐Kun
Zhang, Jin‐San
author_facet Tan, Xiao‐Hua
Zheng, Xiao‐Meng
Yu, Li‐Xia
He, Jian
Zhu, Hong‐Mei
Ge, Xiu‐Ping
Ren, Xiao‐Li
Ye, Fa‐Qing
Bellusci, Saverio
Xiao, Jian
Li, Xiao‐Kun
Zhang, Jin‐San
author_sort Tan, Xiao‐Hua
collection PubMed
description Ischaemia‐reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI‐induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R‐induced acute renal dysfunction and largely blunted I/R‐induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL‐positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro‐apoptotic alteration of Bcl2/Bax expression, caspase‐3 activation, loss of mitochondrial membrane potential and K(ATP) channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the K(ATP) channel blocker 5‐HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post‐I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage‐associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL‐1α, IL‐6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1‐mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI‐induced AKI.
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spelling pubmed-56612602017-11-02 Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling Tan, Xiao‐Hua Zheng, Xiao‐Meng Yu, Li‐Xia He, Jian Zhu, Hong‐Mei Ge, Xiu‐Ping Ren, Xiao‐Li Ye, Fa‐Qing Bellusci, Saverio Xiao, Jian Li, Xiao‐Kun Zhang, Jin‐San J Cell Mol Med Original Articles Ischaemia‐reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI‐induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R‐induced acute renal dysfunction and largely blunted I/R‐induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL‐positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro‐apoptotic alteration of Bcl2/Bax expression, caspase‐3 activation, loss of mitochondrial membrane potential and K(ATP) channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the K(ATP) channel blocker 5‐HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post‐I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage‐associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL‐1α, IL‐6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1‐mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI‐induced AKI. John Wiley and Sons Inc. 2017-05-24 2017-11 /pmc/articles/PMC5661260/ /pubmed/28544332 http://dx.doi.org/10.1111/jcmm.13203 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Tan, Xiao‐Hua
Zheng, Xiao‐Meng
Yu, Li‐Xia
He, Jian
Zhu, Hong‐Mei
Ge, Xiu‐Ping
Ren, Xiao‐Li
Ye, Fa‐Qing
Bellusci, Saverio
Xiao, Jian
Li, Xiao‐Kun
Zhang, Jin‐San
Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
title Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
title_full Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
title_fullStr Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
title_full_unstemmed Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
title_short Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
title_sort fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661260/
https://www.ncbi.nlm.nih.gov/pubmed/28544332
http://dx.doi.org/10.1111/jcmm.13203
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