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

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.

Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury

“…Previous reports have highlighted the significant role of CircRNAs in mediating in renal tubular cell apoptosis during sepsis injury [23,24]. Various CirRNAs such as Circ_35953, Circ_HIPK3, Circ_0114427, CIRC_0114428, Circ_0001714, circ_0020339, Circ_RASGEF1B, Circ_0114428, circ-FANCA, CircNRIP1, circ0001818, and Circ_0001806 [16,23,[25][26][27][28][29][30][31][32][33][34] have been implicated in LPS-induced renal tubular cell apoptosis. Conversely, others such as CircITCH, CircVMA21, CIRC_0008882, and Circ_0091702 [35][36][37][38] exhibit an opposing role.…”

Circvma21-Related Pathway Alleviates Lipopolysaccharide-Induced Hk-2 Cell Injury

“…Studies have shown that a total of 811 differentially expressed circRNAs were identified in the LPS-induced rat model, and a lot of circRNAs play a vital role in the inflammatory response (28). Circ_0114428 knockdown relieved LPS-induced HK2 cell apoptosis and inflammation injury (29). CircUSP42 was downregulated in septic AKI patients, which could ameliorate LPS-induced HK2 cell apoptosis, inflammation and oxidative stress (30).…”