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

Feng, Shengdong; Gao, Lu; Zhang, Dianhong; Tian, Xinyu; Kong, Lingyao; Shi, Huiting; Wu, Leiming; Huang, Zhen; Du, Binbin; Liang, Cui; Zhang, Yanzhou; Yao, Rui

doi:10.7150/ijbs.36995

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Int J Biol Sci 2019; 15(12):2615-2626. doi:10.7150/ijbs.36995 This issue Cite

Research Paper

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

Shengdong Feng^*, Lu Gao^*, Dianhong Zhang^*, Xinyu Tian, Lingyao Kong, Huiting Shi, Leiming Wu, Zhen Huang, Binbin Du, Cui Liang, Yanzhou Zhang^✉, Rui Yao^✉

Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
*Shengdong Feng, Lu Gao and Dianhong Zhang are co-first authors

Citation:

Feng S, Gao L, Zhang D, Tian X, Kong L, Shi H, Wu L, Huang Z, Du B, Liang C, Zhang Y, Yao R. MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. Int J Biol Sci 2019; 15(12):2615-2626. doi:10.7150/ijbs.36995. https://www.ijbs.com/v15p2615.htm

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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.

Keywords: miR-93, vascular smooth muscle cells, proliferation, migration, Mfn2

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APA

Feng, S., Gao, L., Zhang, D., Tian, X., Kong, L., Shi, H., Wu, L., Huang, Z., Du, B., Liang, C., Zhang, Y., Yao, R. (2019). MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. International Journal of Biological Sciences, 15(12), 2615-2626. https://doi.org/10.7150/ijbs.36995.

ACS

Feng, S.; Gao, L.; Zhang, D.; Tian, X.; Kong, L.; Shi, H.; Wu, L.; Huang, Z.; Du, B.; Liang, C.; Zhang, Y.; Yao, R. MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. Int. J. Biol. Sci. 2019, 15 (12), 2615-2626. DOI: 10.7150/ijbs.36995.

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CSE

Feng S, Gao L, Zhang D, Tian X, Kong L, Shi H, Wu L, Huang Z, Du B, Liang C, Zhang Y, Yao R. 2019. MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. Int J Biol Sci. 15(12):2615-2626.

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