miR-92a regulates the expression levels of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 3 via sirtuin 1 signaling in hydrogen peroxide-induced vascular smooth muscle cells

Liu,Peng; Su,Jianfang; Song,Xixi; Wang,Shixiao

doi:10.3892/mmr.2017.7937

miR-92a regulates the expression levels of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 3 via sirtuin 1 signaling in hydrogen peroxide-induced vascular smooth muscle cells

Authors:
- Peng Liu
- Jianfang Su
- Xixi Song
- Shixiao Wang
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Affiliations: Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai 200120, P.R. China, College of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Orthopaedics, Shaanxi Provincial People's Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China, Department of Internal Medicine, Shanghai Dermatology Hospital, Tongji University, Shanghai 200443, P.R. China
Published online on: November 2, 2017 https://doi.org/10.3892/mmr.2017.7937
Pages: 1041-1048

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Abstract

Vascular smooth muscle cells (VSMCs) exhibit a notably increased rate of migration, which is one of the most common pathological changes in atherosclerosis. Investigations into the role of micro (mi)RNAs in the regulation of VSMC migration are beginning to emerge and additional miRNAs involved in VSMC migration modulation require identification. In the current study, VSMCs were primarily cultured from rat thoracic aortas, transfected with miR‑92a mimics and induced by hydrogen peroxide (H2O2) for 24 h. Total mRNA and protein were collected for quantitative polymerase chain reaction and western blot analysis. In addition, the sirtuin 1 (SIRT1) gene was detected by luciferase reporter assay and VSMC migration was detected by Transwell migration assay. The current results demonstrated that reduced expression of miR‑92a and overexpression of SIRT1 at the mRNA level were observed in H2O2‑induced VSMCs. Furthermore, luciferase reporter assay demonstrated that the activity of the SIRT1 3'‑untranslated region was reduced by miR‑92a mimics. The upregulation of MMP9 and the downregulation of TIMP3 in H2O2‑induced VSMCs were observed to be reversed by miR‑92a mimics in addition to SIRT1 siRNA. Finally, Transwell migration assay revealed that miR‑92a overexpression and silencing SIRT1 mitigated VSMC migration following H2O2 treatment. The present study indicated that miR‑92a prevented the migration of H2O2‑induced VSMCs by repressing the expression of SIRT1, and also provided a novel therapy to protect against the phenotypic change of VSMCs in atherosclerosis.

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