Exogenous spexin aggravates renal ischemia reperfusion injury and triggers toxicity in healthy kidneys

Kulualp K., Kumaş Kulualp M., Semen Z., Güvenç Bayram G., Çelik A., Ak M. Y., ...More

FRONTIERS OF MEDICINE, vol.19, no.5, pp.842-854, 2025 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 19 Issue: 5
  • Publication Date: 2025
  • Doi Number: 10.1007/s11684-025-1159-x
  • Journal Name: FRONTIERS OF MEDICINE
  • Journal Indexes: Scopus, Science Citation Index Expanded (SCI-EXPANDED), EMBASE, MEDLINE
  • Page Numbers: pp.842-854
  • Dokuz Eylül University Affiliated: Yes

Abstract

<<<<<<<<<<<<<<<<<<<<<<<<<<<Renalischemia–reperfusioninjury(IRI)isamajorcontributortoacutekidneyinjury(AKI),leading
tosubstantialmorbidityandmortality.Spexin(SPX),a14-aminoacidendogenouspeptideinvolvedinmetabolic
regulationandimmunemodulation,hasnotyetbeenstudiedinthecontextofchronictreatmentandrenalIRI.
This study evaluated the effects of exogenous SPX on renal function, histopathological changes, and molecular
pathways in both IRI-induced injured and healthy kidneys. Twenty-eight male BALB/c mice were divided into
fourgroups:control,SPX,IRI,andSPX+IRI.IRIwasinducedby30minutesofbilateralrenalischemiafollowed
by 6 hours of reperfusion.Renal injury markers, histopathological changes, inflammatory mediators, apoptotic
markers,andfibrosis-relatedproteinswereanalyzed.SPXsignificantlyexacerbatedIRI-inducedkidneyinjuryby
activating the Wnt/β-catenin signaling pathway and promoting the upregulation of pro-inflammatory, pro-
apoptotic, and pro-fibrotic mediators. It is noteworthy that SPX exerted more severe deleterious nephrotoxic
effects in the healthy kidney compared to those observed in the IRI-induced injured kidney. These findings
indicatethatchronictreatmentwithSPXadministrationmayhaveintrinsicpro-inflammatory,pro-apoptoticand
fibrotic properties, raising concerns about its therapeutic potential. Further research is needed to clarify its
physiologicalroleandtherapeuticimplicationsinkidneydiseases.<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<tosubstantialmorbidityandmortality.Spexin(SPX),a14-aminoacidendogenouspeptideinvolvedinmetabolic
regulationandimmunemodulation,hasnotyetbeenstudiedinthecontextofchronictreatmentandrenalIRI.
This study evaluated the effects of exogenous SPX on renal function, histopathological changes, and molecular
pathways in both IRI-induced injured and healthy kidneys. Twenty-eight male BALB/c mice were divided into
fourgroups:control,SPX,IRI,andSPX+IRI.IRIwasinducedby30minutesofbilateralrenalischemiafollowed
by 6 hours of reperfusion.Renal injury markers, histopathological changes, inflammatory mediators, apoptotic
markers,andfibrosis-relatedproteinswereanalyzed.SPXsignificantlyexacerbatedIRI-inducedkidneyinjuryby
activating the Wnt/β-catenin signaling pathway and promoting the upregulation of pro-inflammatory, pro-
apoptotic, and pro-fibrotic mediators. It is noteworthy that SPX exerted more severe deleterious nephrotoxic
effects in the healthy kidney compared to those observed in the IRI-induced injured kidney. These findings
indicatethatchronictreatmentwithSPXadministrationmayhaveintrinsicpro-inflammatory,pro-apoptoticand
fibrotic properties, raising concerns about its therapeutic potential. Further research is needed to clarify its
physiologicalroleandtherapeuticimplicationsinkidneydiseases.