Exogenous spexin aggravates renal ischemia reperfusion injury and triggers toxicity in healthy kidneys.
10.1007/s11684-025-1159-x
- Author:
Kadri KULUALP
1
;
Meltem Kumaş KULUALP
2
;
Zeynep SEMEN
3
;
Gökçen Güvenç BAYRAM
4
;
Aslı ÇELIK
5
;
Melek Yeşim AK
6
;
Osman YILMAZ
5
Author Information
1. Department of Surgery, Faculty of Veterinary Medicine, Dokuz Eylül University, Izmir, 35890, Turkey.
2. Department of Histology and Embryology, Faculty of Veterinary Medicine, Dokuz Eylül University, Izmir, 35890, Turkey. meltem.kumas@deu.edu.tr.
3. Department of Biochemistry, Faculty of Veterinary Medicine, Dokuz Eylül University, Izmir, 35890, Turkey.
4. Department of Physiology, Faculty of Veterinary Medicine, Dokuz Eylül University, Izmir, 35890, Turkey.
5. Multidisciplinary Experimental Animal Laboratory, Faculty of Medicine, Dokuz Eylül University, Izmir, 35410, Turkey.
6. Department of Histology and Embryology, Faculty of Medicine, Dokuz Eylül University, Izmir, 35410, Turkey.
- Publication Type:Journal Article
- Keywords:
Wnt/β-catenin signaling;
apoptosis;
inflammation;
mice (BALB/c);
renal ischemia-reperfusion injury;
spexin
- MeSH:
Animals;
Reperfusion Injury/chemically induced*;
Male;
Mice, Inbred BALB C;
Mice;
Acute Kidney Injury/metabolism*;
Kidney/blood supply*;
Peptide Hormones/adverse effects*;
Apoptosis/drug effects*;
Wnt Signaling Pathway/drug effects*;
Disease Models, Animal
- From:
Frontiers of Medicine
2025;19(5):842-854
- CountryChina
- Language:English
-
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.
