MicroRNA-98-5p inhibits human mesangial cell proliferation and TNF-α and IL‑6 secretion by targeting BTB and CNC homology 1

Abstract

MicroRNA (miR)-98-5p has been reported to be involved in the development of lupus nephritis (LN); however, its specific role in LN remains unclear. The present study aimed to investigate the effect of miR-98-5p on human mesangial cell proliferation and the secretion of TNF-α and IL-6. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to analyze the level of gene and protein expression, respectively. Cellular proliferation was assessed using a Cell Counting Kit-8 (CCK-8) assay. ELISA was used to detect the secretion of TNF-α and IL-6 by human mesangial cells. RT-qPCR analysis revealed that miR-98-5p expression was downregulated in LN renal tissues compared with control renal tissues. Overexpression of miR-98-5p inhibited human mesangial cell proliferation and the secretion of TNF-α and IL-6, whereas miR-98-5p-knockdown demonstrated the opposite effect. Dual luciferase reporter assays demonstrated that miR-98-5p directly targeted BTB and CNC homology 1 (BACH1). BACH1-overexpression promoted human mesangial cell proliferation and the secretion of TNF-α and IL-6, whereas BACH1-knockdown demonstrated the opposite effect. Notably, co-transfection with miR-98-5p mimic inhibited BACH1-overexpression induced human mesangial cell proliferation and the secretion of TNF-α and IL-6. The results of the present study indicated that miR-98-5p inhibited human mesangial cell proliferation and the secretion of TNF-α and IL-6 by targeting BACH1. Therefore, miR-98-5p and BACH1 may represent potential therapeutic targets for LN.

Mesangial cell: A hub in lupus nephritis

“…IgG anti-dsDNA also drive the expansion of MCs through microRNAs, which are short non-coding RNAs that act as guide molecules in RNA silencing by inducing mRNA degradation or blocking protein translation (73). Research has demonstrated that diverse miRNAs are downregulated in LN induced by anti-dsDNA antibodies and could inhibit MCs' proliferation through multiple signaling pathways, including miR-10a, miR-16, miR-124, miR-133, miR-155, miR-98-5p, miR-146b-5p, and hsa−miR−371−5p (74)(75)(76)(77)(78)(79)(80)(81). Further, some miRNAs exert positive regulatory effects on the proliferation of MCs.…”

“…MiR-146b, miR-124, and miR-203 attenuate the inflammatory response of MCs by inhibiting the expression levels of TNF receptor-associated factor 6 (TRAF6) in LN ( 74 , 75 , 107 , 108 ). MiR-98-5p inhibits the secretion of TNF-α and IL-6 by targeting BACH1 in human MCs ( 80 ). Blocking hsa-miR-127-3p could promote the expression of JAK1 and leads to the excessive activation of the IFN-I signaling pathway in LN ( 109 ).…”

Lupus nephritis: The regulatory interplay between epigenetic and MicroRNAs

“…Numerous reviews and preclinical and clinical studies have established and discussed the critical roles of various miRNAs in the development, prognosis, and therapies of LN (Dominguez-Gutierrez et al, 2014;Habibi et al, 2016;Li et al, 2017;Trinh et al, 2017;Zhu et al, 2017;Xu et al, 2018;Ye et al, 2018;Feng et al, 2019;Liu et al, 2019;Qi et al, 2020;Shao et al, 2020;Sun et al, 2020;Abdul-Maksoud et al, 2021;Du et al, 2021;Perez-Hernandez et al, 2021;So et al, 2021;Xu et al, 2021;Zhang et al, 2021). There has been much research and review on the role of miRNAs in LN over the last decade, and several wellknown miRNAs have been linked to the development and progression of LN (Table 1).…”

“…Inflammatory pathways, and that changes in the expression of these miRNAs may be linked to inflammation in LN (Feng et al, 2019;Shao et al, 2020;Du et al, 2021). The critical role of macrophages in inflammatory processes has been well established.…”

“…The critical role of macrophages in inflammatory processes has been well established. A study revealed that miR-98-5p elicits macrophage transformation into the M2 phenotype by directly inhibiting the expression of BTB and CNC homology 1 (BACH1) (Du et al, 2021). In addition, studies also discovered that BACH1 helps cells grow and produce inflammatory factors through NF-κB (Liu et al, 2019;Sun et al, 2020).…”