MiR-760 protects against lipopolysaccharide-induced septic acute kidney injury by targeting ENKD1
- 30.04.2025
- Original article
Erschienen in:
- Verfasst von
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Xinxin Li
Xinxin Li
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Xinxin Li and Jianchao Li equal contribution.
- Department of Emergency Intensive Care Medicine and Emergency Medicine, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, 224000, Yancheng, China
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Jianchao Li
Jianchao Li
-
Xinxin Li and Jianchao Li equal contribution.
- Department of Emergency Intensive Care Medicine and Emergency Medicine, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, 224000, Yancheng, China
-
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Liangliang Zhou
Liangliang Zhou
- Department of Emergency Intensive Care Medicine and Emergency Medicine, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, 224000, Yancheng, China
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Yingbin Li
Yingbin Li
- Department of Emergency Intensive Care Medicine and Emergency Medicine, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, 224000, Yancheng, China
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Xufeng Wu
Xufeng Wu
- Department of Emergency Intensive Care Medicine and Emergency Medicine, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, 224000, Yancheng, China
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Jianjun Chen
Korrespondierender Autor Jianjun Chen
- Department of Emergency Intensive Care Medicine and Emergency Medicine, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, 224000, Yancheng, China
- Erschienen in
- Clinical and Experimental Nephrology | Ausgabe 11/2025
Abstract
Background
Sepsis, a systemic inflammatory disease, often leads to severe complications, including septic acute kidney injury (AKI). Despite its prevalence, effective treatments for septic AKI remain elusive. MicroRNAs (miRNAs) are critical regulators of gene expression and play essential roles in sepsis pathogenesis. This study investigates the function and regulatory pathway of miR-760 in septic AKI.
Methods
Septic AKI models were developed using lipopolysaccharide (LPS)-treated mice and HK-2 renal tubular epithelial cells. Renal pathology was assessed via H&E staining, while renal function was assessed through the measurement of blood urea nitrogen (BUN) and creatinine levels. Apoptosis, inflammation, and oxidative stress markers were analyzed using functional assays, ELISA, and flow cytometry. Bioinformatics analysis, RT-qPCR, and dual luciferase reporter assays were used to identify and validate miR-760’s target, enkurin domain containing 1 (ENKD1).
Results
Database analysis and experimental validation revealed markedly decreased level of miR-760-3p levels in LPS-induced septic AKI mice model. MiR-760-3p overexpression in vivo ameliorated renal damage, improved kidney function, and reduced tubular apoptosis, inflammation, and oxidative stress. In vitro, miR-760 mimics enhanced cell proliferation while inhibiting apoptosis, inflammation, and oxidative stress in LPS-stimulated HK-2 cells. Mechanistically, ENKD1 was identified as a direct target of miR-760. ENKD1 overexpression negated the protective effects of miR-760, exacerbating renal injury, apoptosis, and inflammatory responses.
Conclusion
This study demonstrates that miR-760 alleviates septic AKI by targeting ENKD1, reducing apoptosis, inflammation, and oxidative stress. The miR-760/ENKD1 axis offers a promising therapeutic avenue to address septic AKI.
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- Titel
- MiR-760 protects against lipopolysaccharide-induced septic acute kidney injury by targeting ENKD1
- Verfasst von
-
Xinxin Li
Jianchao Li
Liangliang Zhou
Yingbin Li
Xufeng Wu
Jianjun Chen
- Publikationsdatum
- 30.04.2025
- Verlag
- Springer Nature Singapore
- Erschienen in
-
Clinical and Experimental Nephrology / Ausgabe 11/2025
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799 - DOI
- https://doi.org/10.1007/s10157-025-02690-z
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