CIRC_0114428 INFLUENCES THE PROGRESSION OF SEPTIC ACUTE KIDNEY INJURY VIA REGULATING MIR-370-3P/TIMP2 AXIS

Background: Septic acute kidney injury (AKI) is a serious complication of sepsis, which greatly threatened the life safety of critically ill patients. Recently, circular RNA is considered to be implicated in sepsis-induced renal cell damage. However, the role of circ_0114428 in sepsis AKI is still unclear. Methods: LPS was used to establish a sepsis-related AKI cell model. The expression of circ_0114428, microRNA (miR)-370-3p, tissue inhibitor of metalloproteinase-2 (TIMP2), Proliferating cell nuclear antigen, Bax, and Bcl-2 were detected by quantitative real-time polymerase chain reaction and Western blot. Cell counting kit 8 and enzyme-linked immunosorbent assay were used to measure cell proliferation ability and the secretion of inflammatory factors (tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6), respectively. Cell cycle and apoptosis rate were analyzed by flow cytometry. Caspase-3 assay kits were used to detect Caspase-3 activity. Interaction between miR-370-3p and circ_0114428 or TIMP2 was analyzed by bioinformatics analysis, a dual-luciferase reporter assay, and RNA immunoprecipitation assay. Results: Circ_0114428 was upregulated in septic AKI serum samples and LPS-induced HK2 cells. The knockdown of circ_0114428 notably promoted cell proliferation and cycle, whereas it restrained cell inflammation and apoptosis in LPS-stimulated HK2 cells. Subsequent mechanism analysis revealed that miR-370-3p was a target of circ_0114428, and miR-370-3p inhibition could rescue the effects of circ_0114428 downregulation on LPS-induced cell injury. Meanwhile, TIMP2 was a target gene of miR-370-3p. miR-370-3p mimic could attenuate LPS-induced cell injury, whereas these impacts were overturned by overexpressed TIMP2. Furthermore, circ_0114428 enhanced TIMP2 protein expression by sponging miR-370-3p. Conclusion: Our data demonstrated that circ_0114428 contributed to septic AKI progression by regulating miR-370-3p-mediated TIMP2 expression, which provided a promising target for septic AKI treatment.