Knockdown of Circ_0114428 Alleviates LPS-Induced Hk2 Cell Apoptosis and Inflammation Injury via Targeting Mir-215-5p/Traf6/Nf-Κb Axis in Septic Acute Kidney Injury

Abstract

Background Sepsis is a systemic inflammatory disease that can cause multiple organ damage. Circular RNAs (circRNAs) have been reported to play a regulatory role in sepsis-induced acute kidney injury (AKI), however, the role of circ_0114428 has not been studied. Methods In this study, HK2 cells were treated with different concentrations of lipopolysaccharide (LPS) to induce cell damage, and then the expressions of circ_0114428, microRNA-215-5p (miR-215-5p), tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and western blot examined the Bax and Cleaved-caspase-3 proteins. Cell proliferation was detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and thymidine analog 5-ethynyl-2’-deoxyuridine (EdU) assay. And cell apoptosis was detected by flow cytometry, and the levels of inflammatory factors were detected by ELISA. Results After LPS treatment with different concentrations, we found that LPS at 10 μg/mL had the best effect on HK2 cells. Circ_0114428 was highly expressed in sepsis-AKI patients and LPS-treated HK2 cells. Knockdown of circ_0114428 restored the effects of LPS treatment on proliferation, apoptosis and inflammatory response of HK2 cells. MiR-215-5p was a target of circ_0114428, and TRAF6 was a downstream target of miR-215-5p. Circ_0114428 regulated TRAF6 expression by sponging miR-215-5p in LPS-treated HK2 cells. Circ_0114428 regulated LPS-induced NF-κB signaling in HK2 cells by targeting miR-215-5p/TRAF6 axis. Conclusion Circ_0114428 knockdown abolished the cell proliferation, apoptosis and inflammatory damage in LPS-induced HK2 cells by targeting miR-215-5p/TRAF6/NF-κB.