KDM2B regulates inflammation and oxidative stress of sepsis via targeting NF‐κB and AP‐1 pathways

BACKGROUNDS: The kidney is an easily affected organ with sepsis which is a main underlying cause of acute kidney injury (AKI). Histone‐modifying lysine‐specific demethylase 2B (KDM2B) is involved in numerous pathological processes, such as cell senescence and tumor development. However, the role of KDM2B in sepsis‐induced AKI is unclear. OBJECTS: To investigate the role of KDM2B on cell viability, inflammation and oxidative stress of sepsis‐associated AKI, and the involved signaling pathways. METHODS: An AKI model in vitro was established through lipopolysaccharide (LPS)‐induction in HK‐2 cells. Western blots were performed to evaluate the expression of KDM2B, cyclooxygenase 2 (COX2), inducible nitric oxide synthase (iNOS), p65, c‐Jun and c‐Fos, as well as p65 phosphorylation. Cell viability was measured using CCK‐8 kit. ELISA was performed to analyze the production of layered double hydroxide (LDH), tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐18, vascular cell adhesion molecule‐1 (VCAM‐1), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and H(2)O(2). The qPCR was used to evaluate the transcription level of TNF‐α, IL‐1β, IL‐18, and VCAM‐1. RESULTS: KDM2B knockdown alleviated LPS‐induced cytotoxicity, decreased LDH release, and improved cell viability. KDM2B knockdown reduced concentration of inflammation‐related molecules including TNF‐α, IL‐1β, IL‐18, and VCAM‐1, and inhibited their transcription. Moreover, KDM2B knockdown promoted the quantity of SOD and GSH, while declined the production of MDA, H(2)O(2), COX2, and iNOS. Further, KDM2B played a role in LPS‐induced HK‐2 cell injury by activating nuclear factor κB (NF‐κB) and activator protein 1 (AP‐1) pathways. CONCLUSION: KDM2B knockdown reduced cytotoxicity, inflammation and oxidative stress in LPS‐induced AKI via inhibiting NF‐κB and AP‐1 pathways, indicating KDM2B may be a promising therapeutic target for the treatment of sepsis‐associated AKI.