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. 2023 Mar 1;59(3):426-433.
doi: 10.1097/SHK.0000000000002057. Epub 2023 Jan 8.

CircNRIP1 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HUMAN KIDNEY 2 CELL APOPTOSIS AND INFLAMMATION THROUGH miR-339-5p/OXSR1 PATHWAY

Pei Li  1 , Yu Liu  2 , Ting You  2
Affiliations

CircNRIP1 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HUMAN KIDNEY 2 CELL APOPTOSIS AND INFLAMMATION THROUGH miR-339-5p/OXSR1 PATHWAY

Pei Li et al. Shock. .

Abstract

Background: CircRNA regulates sepsis-induced acute kidney injury (AKI). CircNRIP1 is overexpressed in the blood of AKI patients, but its role in septic AKI occurrence remains unknown. Methods: Human kidney 2 (HK2) cells were stimulated using lipopolysaccharide (LPS) to generate a septic AKI cell model. The expression levels of circNRIP1, miR-339-5p, oxidative stress-responsive kinase 1 (OXSR1), B-cell lymphoma-2 (Bcl2), BCL2-associated x protein (Bax), and cleaved-caspase 3 were detected by quantitative real-time polymerase chain reaction or Western blotting analysis. Cell viability and apoptosis were investigated by cell counting kit-8 and flow cytometry analysis. The release of proinflammatory cytokines was monitored using commercial kits. The associations among circNRIP1, miR-339-5p, and OXSR1 were identified by mechanism assays. Results: CircNRIP1 was dramatically upregulated in the blood of septic AKI patients and LPS-induced HK2 cells. CircNRIP1 depletion protected HK2 cells from LPS-induced apoptosis and inflammation. MiR-339-5p expression was downregulated in the blood of septic AKI patients, and miR-339-5p combined with circNRIP1. Moreover, circNRIP1 knockdown-induced effects involved the upregulation of miR-339-5p in LPS-treated HK2 cells. Comparatively, OXSR1 expression was increased in the blood of septic AKI patients. MiR-339-5p bound to OXSR1, and circNRIP1 modulated OXSR1 expression by interacting with miR-339-5p. Further, ectopic expression of OXSR1 relieved circNRIP1 knockdown-mediated effects in LPS-induced HK2 cells. Conclusion: CircNRIP1 depletion ameliorated LPS-induced HK2 cell damage by regulating the miR-339-5p/OXSR1 pathway.

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Conflict of interest statement

The authors report no conflicts of interest.

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