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 in vitro. The serum samples of LN patients and normal volunteers were collected. HK-2 cells were challenged via LPS. miR-146b-5p and interferon-induced protein 35 (IFI35) abundances were detected via quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The inflammatory response was assessed via inflammatory cytokines levels via qRT-PCR and enzyme-linked immunosorbent assay. Cell apoptosis was analysed via flow cytometry and apoptotic protein levels. The protein levels of JAK1/STAT1 signalling were detected via western blot. The relationship of miR-146b-5p and IFI35 was analysed via 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 via 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.

Keywords:

• Lupus nephritis
• IFI35
• miR-146b-5p
• inflammatory response
• apoptosis

Ethical approval

All subjects have provided the informed consents. This research has been permitted via the Ethics Committee of Hunan Provincial People’s Hospital.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work is supported by Natural Science Foundation of Hunan Province [2018JJ6017]; Hunan Provincial Health Planning Commission Research Project [B20180563], Changsha Science and Technology Planning Project (No. kq1901058).