Internal medicine

Downregulation and upregulation

Cell

Biotechnology

Receptor

In vivo

Neointimal hyperplasia

Stent

Intimal hyperplasia

PDGFB

Smooth muscle

Biology

Gene

Endocrinology

Cell migration

Platelet-derived growth factor receptor

Chemistry

Cyclin D1

Growth factor

Western blot

Restenosis

Cell cycle

Vascular smooth muscle

Cell growth

Cell biology

Cancer research

Biochemistry

Medicine

International Journal of Biological Sciences

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