Circ-BNIP3L knockdown alleviates LPS-induced renal tubular epithelial cell injury during sepsis-associated acute kidney injury by miR-370-3p/MYD88 axis

Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication of the critically ill patient with high morbidity and mortality. Thus, the goal of this study was to investigate the role of circular RNA BCL2 Interacting Protein 3 Like (circ-BNIP3L) in the pathophysiological mechanism of SA-AKI. The SA-AKI cell model was established by using lipopolysaccharide (LPS)-induced HK-2 cells in vitro. Cell survival was analyzed using cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry and Western blot, respectively. Levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) were detected using ELISA analysis. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were examined using commercial kits. Levels of genes and proteins were detected by qRT-PCR and Western blot. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to identify the target relationship between miR-370-3p and circ-BNIP3L or MYD88 (myeloid differentiation primary response 88). Circ-BNIP3L was highly expressed in SA-AKI patients and LPS-induced HK-2 cells. Silencing of circ-BNIP3L attenuated LPS-induced growth inhibition, inflammation, and oxidative stress in HK-2 cells. Mechanistically, circ-BNIP3L competitively bound to miR-370-3p to up-regulate the expression of its target MYD88. Moreover, miR-370-3p inhibition reversed the beneficial effects of circ-BNIP3L knockdown on LPS-stimulated HK-2 cells. Meanwhile, miR-370-3p overexpression abolished LPS-induced injury in HK-2 cells, which was counteracted by MYD88 up-regulation. Circ-BNIP3L knockdown alleviated LPS-induced renal tubular epithelial cell injury by miR-370-3p/MYD88 axis, opening up a completely new avenue for the treatment of sepsis-associated AKI.