Protective effect of Fenofibrate in renal ischemia reperfusion injury: Involved in suppressing kinase 2 (JAK2)/transcription 3 (STAT3)/p53 signaling activation

Pathol Biol (Paris). 2015 Dec;63(6):236-42. doi: 10.1016/j.patbio.2015.07.010. Epub 2015 Sep 2.

Abstract

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.

Materials and 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.

Conclusion: 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.

Keywords: Apoptose; Apoptosis; Fenofibrate; Fénofibrate; Ischemia/reperfusion injury; JAK2/STAT3/p53; Lésions d’ischémie-reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoprotection / drug effects*
  • Fenofibrate / pharmacology*
  • Janus Kinase 2 / metabolism
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / metabolism
  • Kidney Diseases / prevention & control*
  • Kidney Function Tests
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tumor Suppressor Protein p53
  • Jak2 protein, mouse
  • Janus Kinase 2
  • Fenofibrate