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Updated: Aug 31, 2025
Technical Refinement of a Bilateral Renal Ischemia-Reperfusion Mouse Model for Acute Kidney Injury Research
Published on: November 3, 2023
Alpha-NETA, as a CMKLR1 Small Molecule Antagonist, Protects against Renal Ischemia Reperfusion Injury in Mice
Xue Peng1, Wenjuan Wang1, Wenhao Wang1
1Department of Gerontology, Cangzhou Central Hospital, No.16 Xinhua West Road, Cangzhou, Hebei 061000, China.
Background:
Ischemia-reperfusion (IR) injury is one of the major causes of acute kidney injury (AKI). Chemerin chemokine-like receptor 1 (CMKLR1) has been reported to be involved in the progression of IR injury. Here, we investigated the protective role of CMKLR1 antagonist, α-NETA, in IR mouse model, and dissected the underlying regulatory mechanism.
Methods:
IR injury mouse model was established to evaluate the protective effects of α-NETA on IR injury. Kidney injury-associated parameters and functions were examined to evaluate the renal function of Sham, IR, and IR+ α-NETA mice. Renal morphological changes and apoptosis were determined by PAS and TUNEL staining in IR and α-NETA treated mice. ELISA, RT-qPCR, and western blot were performed to examine the inflammatory responses and expression of CMKLR1.
Results:
α-NETA administration attenuated IR-induced renal tubular injury and epithelial cell apoptosis in IR injury mice. Kidney injury-related cystatin C, kidney injury molecule-1, neutrophil gelatinaseassociated lipocalin, and renal morphology were significantly improved. Mechanistically, α-NETA suppressed the inflammatory responses by inhibiting the expression of CMKLR1, and then protected the IR-induced renal damage and restored renal function.
Conclusion:
CMKLR1 plays an important role in renal ischemia-reperfusion injury, targeting CMKLR1 by using the small molecule inhibitor α-NETA is a potential treatment strategy for AKI.
Insights
CMKLR1 antagonist α-NETA protects against kidney ischemia-reperfusion (IR) injury by reducing inflammation and apoptosis. This suggests CMKLR1 targeting is a promising strategy for acute kidney injury (AKI) treatment.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Ischemia-reperfusion (IR) injury is a primary cause of acute kidney injury (AKI).
- Chemerin chemokine-like receptor 1 (CMKLR1) is implicated in the progression of IR injury.
- Investigating CMKLR1's role and potential therapeutic interventions is crucial for AKI management.
Purpose of the Study:
- To evaluate the protective effects of the CMKLR1 antagonist, α-NETA, in a mouse model of IR injury.
- To elucidate the underlying mechanisms by which α-NETA exerts its protective effects.
- To assess the therapeutic potential of targeting CMKLR1 for AKI.
Main Methods:
- Establishment of an IR mouse model to assess α-NETA's efficacy.
- Evaluation of renal function using kidney injury biomarkers (cystatin C, KIM-1, NGAL) and morphological analysis (PAS staining).
- Assessment of apoptosis via TUNEL staining and examination of inflammatory responses and CMKLR1 expression using ELISA, RT-qPCR, and Western blot.
Main Results:
- α-NETA administration significantly reduced IR-induced renal tubular injury and epithelial cell apoptosis.
- Treatment with α-NETA led to marked improvements in kidney injury markers and renal morphology.
- Mechanistically, α-NETA suppressed inflammatory responses by inhibiting CMKLR1 expression, thereby protecting against renal damage and restoring function.
Conclusions:
- CMKLR1 plays a significant role in the pathogenesis of renal IR injury.
- Targeting CMKLR1 with small molecule inhibitors like α-NETA presents a potential therapeutic strategy for AKI.
- Further research into CMKLR1-targeted therapies could lead to novel treatments for kidney diseases.
