Protective effect of Fenofibrate in renal ischemia reperfusion injury: Involved in suppressing kinase 2 (JAK2)/transcription 3 (STAT3)/p53 signaling activation.
OBJECTIVE
Renal ischemia reperfusion (I/R) injury is a common reason of acute kidney injury. Apoptosis play an important role in the IRI. Fenofibrate, one of agonist Peroxisome proliferator-activated receptor-alpha (PPARα) has the effect of anti-apoptosis. This study was to explore the effect of Fenofibrate on renal ischemia reperfusion injury and its mechanism.


METHODS
IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion for 24h. Eighteen male C57BL/6 mice were randomly divided into three groups: Sham group (Sham), IRI group (IRI), I/R-Fenofibrate group (FEN). Fenofibrate was injected at 45 min before renal ischemia. Renal histology, function, and the expression of Bax, Bcl-2, Bcl-xl p21, p53, Caspase3, CytC, p-JAK2, p-STAT3 and p-PPAR-α were assessed.


RESULTS
Fenofibrate precondition can significantly alleviate the renal dysfunction, the pathological change, up-regulate the expression of p-PPAR-α, Bcl-2, Bcl-xl, Caspase3 and down-regulate the expression of p-JAK2, p-STAT3, p53, p21, CytC and Bax induced by renal IR injury.


CONCLUSIONS
Fenofibrate precondition can protect mice against IRI by suppressing p53-mediating apoptosis which was associated with inhibiting JAK2/STAT3 signaling activation though further activating PPAR-α. Our findings suggest that Fenofibrate could be useful for preventing IR-induced renal injury.
Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Nephrology, Guangzhou, People's Republic of China. Electronic address: bingbinglv@126.com.
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Lv
Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Nephrology, Guangzhou, People's Republic of China.
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X
Wang
Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Research Center of Medicine, Guangzhou, People's Republic of China.
S Y
SY
Liu
Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Nephrology, Guangzhou, People's Republic of China.
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PF
Liang
Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Nephrology, Guangzhou, People's Republic of China.
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M
Feng
Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Nephrology, Guangzhou, People's Republic of China.
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LL
Zhang
Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital, Department of Nephrology, Guangzhou, People's Republic of China.
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AP
Xu
D000818:Animals; D019610:Cytoprotection / Q000187:drug effects*; D011345:Fenofibrate / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016159:Tumor Suppressor Protein p53; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D011345:Fenofibrate
Apoptose; Apoptosis; Fenofibrate; Fénofibrate; Ischemia/reperfusion injury; JAK2/STAT3/p53; Lésions d’ischémie-reperfusion