miR-634 inhibits human vascular smooth muscle cell proliferation and migration in hypertension through Wnt4/𝜷-catenin pathway

³ Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, 710061 Xi’an, Shaanxi, China

^*Correspondence: ykang@mail.xjtu.edu.cn (Yuming Kang)

Front. Biosci. (Landmark Ed) 2021, 26(8), 395–404; https://doi.org/10.52586/4953

Submitted: 16 March 2021 | Revised: 5 July 2021 | Accepted: 7 July 2021 | Published: 30 August 2021

This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Abstract

MicroRNAs (miRNAs) have been regarded as modulators in vascular pathologies, including hypertension. Dysregulated proliferation and migration of VSMCs (vascular smooth muscle cells) contributes to vascular remodeling during hypertension. miR-634 was reported to be dysregulated in hypertensive patients. The involvement of miR-634 in hypertension and the role of miR-634 on VSMCs proliferation and migration were then evaluated. Firstly, HASMCs (human aortic smooth muscle cells) were incubated with 2 $\mu{}$ M angiotensin (Ang) II for 12 hours to establish the cell model of Ang II-induced hypertension. Results showed that Ang II treatment promoted proliferation and migration of HASMCs. Secondly, miR-634 was down-regulated in the hypertensive patients, and reduced in Ang II-induced HASMCs in a time dependent manner. Functional assays revealed that Ang II promoted proliferation and migration of HASMCs were suppressed by miR-634 mimic. Lastly, miR-634 targeted 3 ${{}^{\prime}}$ untranslated region (UTR) of Wnt4, and reduced Wnt4 expression in HASMCs. miR-634 inhibited $\beta{}$ -catenin nuclear translocation. Over-expression of Wnt4 counteracted the suppressive effects of miR-634 on Ang II-induced proliferation and migration of HASMCs. In conclusion, miR-634 inhibited HASMCs proliferation and migration through inactivation of Wnt4/ $\beta{}$ -catenin pathway.

Keywords

HASMCs

miR-634

Migration

Proliferation

Wnt4/

\beta{}

-catenin

Hypertension

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Fig. 1.

miR-634 was reduced in Ang II-induced HASMCs.
(A) The effect of 2 $\mu{}$ M Ang II on cell proliferation of HASMCs was detected by EdU staining. (B) The effect of 2 $\mu{}$ M Ang II on cell migration of HASMCs was detected by transwell. (C) Invasion cells number affected by Ang II treatment. (D) The effect of 2 $\mu{}$ M Ang II on miR-634 expression of HASMCs in different time. ** p $<$ 0.01. Scale bars: 50 $\mu{}$ m.

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