MiR-146b-5p targets IFI35 to inhibit inflammatory response and apoptosis via JAK1/STAT1 signalling in lipopolysaccharide-induced glomerular cells

Abstract

The dysregulated microRNAs (miRNAs) are implicated in the malignancy of lupus nephritis (LN). This work aims to analyse the effect and mechanism of miR-146b-5p in lipopolysaccharides (LPS)-induced model of LN <i>in vitro</i>. The serum samples of LN patients and normal volunteers were collected. HK-2 cells were challenged <i>via</i> LPS. miR-146b-5p and interferon-induced protein 35 (IFI35) abundances were detected <i>via</i> quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The inflammatory response was assessed <i>via</i> inflammatory cytokines levels <i>via</i> qRT-PCR and enzyme-linked immunosorbent assay. Cell apoptosis was analysed <i>via</i> flow cytometry and apoptotic protein levels. The protein levels of JAK1/STAT1 signalling were detected <i>via</i> western blot. The relationship of miR-146b-5p and IFI35 was analysed <i>via</i> bioinformatics and dual-luciferase reporter assays. This study revealed that miR-146b-5p level was declined and IFI35 abundance was elevated in serum of LN patients and LPS-challenged HK-2 cells. Functionally, IFI35 overexpression promoted LPS-caused inflammatory response and cell apoptosis, and knockdown of IFI35 caused an opposite trend. Meanwhile, miR-146b-5p targeted IFI35 to suppress inflammatory response and cell inflammatory response and apoptosis <i>via</i> inactivating the JAK1/STAT1 pathway. MiR-146b-5p suppressed inflammatory response and cell apoptosis by IFI35 mediated-JAK1/STAT1 signalling in HK-2 cells, which provided a new mechanism for understanding the pathogenesis of LN.