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., ...Daha Fazla

FRONTIERS OF MEDICINE, cilt.19, sa.5, ss.842-854, 2025 (SCI-Expanded)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19 Sayı: 5
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s11684-025-1159-x
  • Dergi Adı: FRONTIERS OF MEDICINE
  • Derginin Tarandığı İndeksler: Scopus, Science Citation Index Expanded (SCI-EXPANDED), EMBASE, MEDLINE
  • Sayfa Sayıları: ss.842-854
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

<<<<<<<<<<<<<<<<<<<<<<<<<<<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.