LncRNA NKILA knockdown promotes cell viability and represses cell apoptosis, autophagy and inflammation in lipopolysaccharide-induced sepsis model by regulating miR-140-5p/CLDN2 axis

Abstract

Background: Long non-coding RNAs (lncRNAs) play vital roles in human diseases, including sepsis-induced acute kidney injury (AKI). Here, we aimed to investigate the functions of lncRNA NKILA in sepsis-engendered AKI.

Methods: HK2 cells stimulated with LPS were used to mimic sepsis-induced AKI in vitro. qRT-PCR was conducted for lncRNA NKILA and miR-140-5p levels. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were employed to analyze cell viability and apoptosis. Western blot assay was utilized to measured protein levels. ELISA kits were used to examine the concentrations of IL-6, IL-1β and TNF-α. Dual-luciferase reporter assay was utilized to analyze the relationships among lncRNA NKILA, miR-140-5p and claudin 2 (CLDN2).

Results: LPS restrained HK2 cell viability and accelerated cell apoptosis and autophagy. LncRNA NKILA was increased in LPS-treated HK2 cells. LncRNA NKILA silencing reversed the promotional influence of LPS on cell progression in HK2 cells. miR-140-5p inhibition ameliorated lncRNA NKILA knockdown-mediated cell injury in LPS-mediated HK2 cells. CLDN2 was the target of miR-140-5p. MiR-140-5p elevation promoted cell viability and suppressed cell apoptosis, autophagy and inflammation in LPS-induced HK2 cells, with CLDN2 elevation overturned the effects.

Conclusion: LncRNA NKILA silencing protected HK2 cells from LPS-induced impairments by reducing CLDN2 through sponging miR-140-5p.

Keywords: CLDN2; HK2; LPS; lncRNA NKILA; miR-140-5p.