2. Academic Validation
  3. Apelin-13 alleviated ischemia reperfusion injury via KLF2/NF-κB signaling pathway after kidney transplantation

Apelin-13 alleviated ischemia reperfusion injury via KLF2/NF-κB signaling pathway after kidney transplantation

  • Int Immunopharmacol. 2026 Jan 1;168(Pt 1):115802. doi: 10.1016/j.intimp.2025.115802.
Jie Zhang 1,  Chengjun Yu 1,  Huyu Wang 1,  Hanyu Xiao 1,  Sheng Wen 1,  Yi Hua 2,  Guanghui Wei 3
Affiliations

Affiliations

  • 1 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, Chongqing, China.
  • 2 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, Chongqing, China. Electronic address: [email protected].
  • 3 Department of Urology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Children Urogenital Development and Tissue Engineering of Chongqing Education Commission of China, Chongqing, China. Electronic address: [email protected].
PMID: 41223609 DOI: 10.1016/j.intimp.2025.115802
Abstract

Kidney transplantation (KT) represents the optimal treatment method for chronic kidney disease. However, various acute and chronic injuries seriously compromise the long-term survival rates of grafts and patients. Ischemia-reperfusion injury (IRI), which is inevitable in KT, initiates damage and inflammatory response in the allografts, leading to delayed graft function, and an increased risk of acute rejection, severely damage the transplanted kidney. The APJ/apelin system has been confirmed to exert an anti-inflammatory effect in multiple organ systems. In this study, a syngeneic orthotopic rat kidney transplantation model was used to simulate the clinical kidney transplantation process to investigate whether apelin-13 mitigates IRI-induced renal damage after KT. Our research results showed that apelin was mainly localized in the renal cortex and its expression decreased after IRI. Compared with the model group, the administration of apelin-13 could improve kidney function, alleviate histological injury scores and tubular architectural disruption, and cell Apoptosis. Importantly, apelin-13 reduced the expression levels of pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Additionally, apelin-13 significantly attenuated the cortical infiltration of T cells, M1 polarized macrophage and neutrophils relative to model group. The classical inflammatory signaling pathway, NF-κB, plays an indispensable role in IRI. In vitro studies were performed using lipopolysaccharide (LPS) as specific NF-κB Agonist. Apelin-13 alleviated the injury and inflammatory response of HK-2 cells induced by LPS. Both in vivo and in vitro experiments confirmed that apelin-13 could suppresses the activation of the NF-κB signaling pathway by upregulating Krüppel-like factor 2 (KLF2). In conclusion, apelin-13 alleviates the inflammatory response triggered by ischemia-reperfusion injury after KT partly through the KLF2/NF-κB signaling pathway.

Keywords

Apelin-13; Ischemia reperfusion injury; Kidney transplantation; Nuclear factor-kappa B.

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