MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2

Abstract

Background/Aims: Vascular smooth muscle cell (VSMC) hyperplasia plays important roles in the pathogenesis of many vascular diseases, such as atherosclerosis and restenosis. Many microRNAs (miRs) have recently been reported to regulate the proliferation and migration of VSMC. In the current study, we aimed to explore the function of miR-93 in VSMCs and its molecular mechanism.Methods: First, qRT-PCR and immunofluorescence assays were performed to determine miR-93 expression in rat VSMCs following carotid artery injury in vivo and platelet-derived growth factor-BB (PDGF-BB) stimulation in vitro. Next, the biological role of miR-93 in rat VSMC proliferation and migration was examined in vivo and vitro. EdU incorporation assay and MTT assay for measuring cell proliferation, Transwell cell invasion assay and Cell scratch wound assay for measuring cell migration. Then, the targets of miR-93 were identified. Finally, the expression levels of proteins in the Raf-ERK1/2 pathway were measured by western blot.Results: MiR-93 was upregulated in rat VSMCs following carotid artery injury in vivo. Similar results were observed in ex vivo cultured VSMCs after PDGF-BB treatment. MiR-93 inhibition suppressed neointimal formation after carotid artery injury. Moreover, our results demonstrated that a miR-93 inhibitor suppressed the PDGF-BB induced proliferation and migration of in VSMC. This inhibitor also decreased the expression levels of MMP2 and cyclin D1. Mechanistically, we discovered that mitofusin 2(Mfn2) is a direct target of miR-93. Furthermore, an analysis of the signaling events revealed that miR-93-mediated VSMC proliferation and migration occurred via the Raf-ERK1/2 pathway.Conclusions: Our findings suggest that miR-93 promotes VSMCs proliferation and migration by targeting Mfn2. MiR-93 may be a new target for treating in-stent restenosis.

MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

“…4c) and that Mfn2 can perform as a target gene for miR-214-3p to regulate cell proliferation. These results are consistent with previous reports, for instance, where Feng et al [39] reported that miR-93 regulates vascular smooth muscle cell proliferation by targeting Mfn2. Additionally, miR-497 promotes cardiomyocyte proliferation by downregulating the expression of Mfn2 [40].…”

miRNA Profiling of Circulating Small Extracellular Vesicles From Subarachnoid Hemorrhage Rats Using Next-Generation Sequencing

“…Previously, miR-15b promoted platelet-derived growth factor signaling, thereby increasing the proliferation of vascular smooth muscle cells ( Kim and Kang, 2013 ). Consistently, recent research shows that miR-93 promotes migration and proliferation of VSMCs targeting Mfn2 ( Feng et al, 2019 ). Additionally, let-7g and miR-98 protected the blood–brain barrier in the context of neuroinflammation ( Rom et al, 2015 ).…”

MicroRNA‑24 attenuates diabetic vascular remodeling by�suppressing the NLRP3/caspase‑1/IL‑1β signaling pathway

“…MicroRNAs (miRNAs/miRs) control diverse cellular functions by negatively modulating the expression of genes. A large number of studies have confirmed that dysregulated miRNAs are involved in the development of neointimal hyperplasia (9)(10)(11)(12). Evidence has demonstrated that the expression of miR-24 differs significantly between patients with atherosclerosis and age-matched controls, whereas overexpression of miR-24 can suppress the development of atherosclerosis (13).…”