MiR‐145‐5p inhibits proliferation and inflammatory responses of RMC through regulating AKT/GSK pathway by targeting CXCL16

Abstract

The main pathological characteristics of chronic glomerulonephritis (CGN) are diffuse mesangial cells proliferation and inflammatory responses. Our previous studies have confirmed that miR-145-5p was abnormally elevated in CGN rats, but its mechanism remains unclear. Therefore, this study aimed to elucidate the mechanism of miR-145-5p in regulation of renal mesangial cells proliferation and inflammatory responses. In vivo study, the cationic bovine serum albumin (C-BSA)-induced CGN rat model was established, and the content of miR-145-5p in renal was examined by qRT-PCR, meanwhile, we also determined the renal function and inflammatory infiltrate. In vitro, the cell proliferation rate, cell cycle and inflammatory changes of rat mesangial cells (RMCs) were measured. Our results suggested that miR-145-5p extended the G0-G1 phase, shortened S phase, inhibited cell proliferation and suppressed inflammatory responses in RMCs. Moreover, miR-145-5p inhibited CXCL16 protein expression through binding the 3'-UTR of CXCL16, suppressed AKT/GSK signaling pathway, and decreased expression of inflammation related mRNAs, such as IL-1α, IL-2, IL-6, and TNF-α mRNAs. Further, locking CXCL16 alleviated inflammatory reactions and down-regulated AKT/GSK pathway in RMCs. Above all, we concluded that miR-145-5p inhibited proliferation and inflammatory responses of RMCs through regulation of AKT/GSK pathway by targeting CXCL16.

Retracted: miR‐145 eliminates lipopolysaccharides‐induced inflammatory injury in human fibroblast‐like synoviocyte MH7A cells

“…The importance of miR-145 in the immune system has been sporadically studied. 28 We demonstrated that miR-145 overexpression had no impact on the release of IL-1β, IL-6, IL-8, and TNF-α in the LPS-untreated MH7A cells, but it could reduce the release of these pro-inflammatory cytokines in LPS-stimulated MH7A cells. 28 Moreover, miR-145 was reported to exert anti-inflammatory functions via inhibiting the expression of pro-inflammatory cytokines IL-1α, IL-2, IL-6, and TNF-α.…”

“…28 Moreover, miR-145 was reported to exert anti-inflammatory functions via inhibiting the expression of pro-inflammatory cytokines IL-1α, IL-2, IL-6, and TNF-α. 28 We demonstrated that miR-145 overexpression had no impact on the release of IL-1β, IL-6, IL-8, and TNF-α in the LPS-untreated MH7A cells, but it could reduce the release of these pro-inflammatory cytokines in LPS-stimulated MH7A cells. Collectively, our finding suggested that miR-145 could protect MH7A cells against LPS-induced inflammatory injury.…”

Downregulation of miR‐145‐5p contributes to hyperproliferation of keratinocytes and skin inflammation in psoriasis

“…It is now widely accepted that the IL‐23–IL‐17A axis plays a central role in the development of psoriasis. Several studies have shown that miR‐145‐5p inhibits cell proliferation and immune responses . We identified a protective association of miR‐145‐5p with psoriasis, and downregulation of miR‐145‐5p contributes to keratinocyte proliferation and skin inflammation.…”

“…In this study we performed a miRNA microarray and found that miR‐145‐5p was downregulated in psoriasis. Recent studies suggest that miR‐145‐5p suppresses inflammation in several inflammatory diseases . The potential regulatory mechanisms of miR‐145‐5p have been investigated, and miR‐145‐5p was shown to regulate inflammatory diseases by modulating various signalling pathways, such as the Akt–glycogen synthase kinase pathway, the mitogen‐activated protein kinase signalling pathway and the mammalian target of rapamycin–nuclear factor (NF)‐κB signalling pathway …”

An integrated analysis of the circRNA–miRNA–mRNA network reveals novel insights into potential mechanisms of cell proliferation during liver regeneration

“…However, Si-circ_19698-1 also led to the obvious down-regulation of Tnfrsf21 (the linear host gene for circ_19698). TNFRSF21, also called death receptor 6 (DR6), belongs to the tumor necrosis factor receptor super-family, and is often reported to induce cell apoptosis [54,55], or inhibit the proliferation and invasion of head and neck squamous cell carcinoma cells [56]. Therefore, TNFRSF21 likely exhibited a reduced inhibitory effect on the proliferation of BRL3A cells and antagonized the inhibitory role of Si-circ_19698-1 during BRL3A proliferation, once its expression was decreased by Si-circ_19698-1.…”