Journal Article

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

Ge, Xiu‐Ping, Ye, Fa‐Qing, Li, Xiao‐Kun, Zheng, Xiao‐Meng, Tan, Xiao‐Hua, Ren, Xiao‐Li, Zhang, Jin‐San, Zhu, Hong‐Mei, He, Jian, Yu, Li‐Xia, Bellusci, Saverio, Xiao, Jian

2017

Overview

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 KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP 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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: acute kidney injury / Acute Kidney Injury - drug therapy / Acute Kidney Injury - genetics / Acute Kidney Injury - metabolism / Acute Kidney Injury - pathology / Animals / Apoptosis / Apoptosis - drug effects / Apoptosis - genetics / bcl-2-Associated X Protein - genetics / bcl-2-Associated X Protein - metabolism / Blood Urea Nitrogen / Caspase / Caspase 3 - genetics / Caspase 3 - metabolism / Caspase-3 / Creatinine / Creatinine - blood / Fibroblast growth factor 2 / Fibroblast Growth Factor 2 - pharmacology / Fibroblast growth factor receptors / Fibroblasts / Gene Expression Regulation / Growth factors / High‐mobility group box 1 / HMGB1 protein / Inflammation / inflammatory cytokine / Interleukin 1 / Interleukin 6 / Interleukins - genetics / Interleukins - metabolism / ischaemia‐reperfusion / Ischemia / Kidney - drug effects / Kidney - metabolism / Kidney - pathology / Male / Membrane potential / Membrane Potential, Mitochondrial - drug effects / Mitochondria / Mitochondria - drug effects / Mitochondria - metabolism / Mitochondria - pathology / mitochondrial dysfunction / Myocardial infarction / Original / Potassium Channels - genetics / Potassium Channels - metabolism / Protective Agents - pharmacology / Proto-Oncogene Proteins c-bcl-2 - genetics / Proto-Oncogene Proteins c-bcl-2 - metabolism / Rats / Rats, Sprague-Dawley / Receptor mechanisms / Receptor, Fibroblast Growth Factor, Type 2 - genetics / Receptor, Fibroblast Growth Factor, Type 2 - metabolism / Renal function / Reperfusion / Reperfusion Injury - drug therapy / Reperfusion Injury - genetics / Reperfusion Injury - metabolism / Reperfusion Injury - pathology / Rodents / Signal Transduction / Tumor necrosis factor / Tumor Necrosis Factor-alpha - genetics / Tumor Necrosis Factor-alpha - metabolism / Urea