Erythropoietin alleviates lung ischemia-reperfusion injury by activating the FGF23/FGFR4/ERK signaling pathway

PeerJ. 2024 Mar 27:12:e17123. doi: 10.7717/peerj.17123. eCollection 2024.

Abstract

Background: The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI).

Methods: Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study.

Results: It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher.

Conclusion: EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.

Keywords: Erythropoietin; FGF23; Lung ischemia-reperfusion injury.

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Epoetin Alfa / metabolism
  • Erythropoietin* / pharmacology
  • Humans
  • Ischemia
  • Lung / metabolism
  • MAP Kinase Signaling System
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Fibroblast Growth Factor, Type 4 / genetics
  • Reperfusion Injury* / drug therapy
  • Signal Transduction
  • bcl-2-Associated X Protein / metabolism

Substances

  • bcl-2-Associated X Protein
  • Caspase 3
  • Epoetin Alfa
  • Erythropoietin
  • FGFR4 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, Fibroblast Growth Factor, Type 4
  • EPO protein, human
  • erythropoietin, rat

Grants and funding

This study was funded by the Basic Public Welfare Research Program of Zhejiang Province (LGF22H010015). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.