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Micro RNA-217 suppresses homocysteine-induced proliferation and migration of vascular smooth muscle cells via N-methyl-D-aspartic acid receptor inhibition.
- Source :
- Clinical & Experimental Pharmacology & Physiology; Oct2016, Vol. 43 Issue 10, p967-975, 9p, 1 Chart, 4 Graphs
- Publication Year :
- 2016
-
Abstract
- Hyperhomocysteine has become a critical risk for atherosclerosis and can stimulate proliferation and migration of vascular smooth muscle cells ( VSMCs). N-methyl-D-aspartic acid receptor ( NMDAR) is a receptor of homocysteine and mediates the effects of homocysteine on VSMCs. Bioinformatics analysis has shown NMDAR is a potential target of micro RNA-217 (miR-217), which exerts multiple functions in cancer tumorigenesis and carotid plaque progression. In this study, we sought to investigate the role of miR-217 in VSMCs phenotype transition under homocysteine exposure and elucidate its effect on atherosclerotic plaque formation. After treating with several doses of homocysteine (0-8 × 10<superscript>−4</superscript> mol/L) for 24 hours, the expression of miR-217 in HA- VSMCs and rat aortic VSMCs was not altered. Intriguingly, the expression of NMDAR mRNA and protein was reduced by homocysteine in a dose-dependent manner. Transfection of miR-217 mimic significantly inhibited the proliferation and migration of VSMCs with homocysteine treatment, while transfection of miR-217 inhibitor promoted VSMCs migration. Moreover, miR-217 mimic down-regulated while miR-217 inhibitor up-regulated NMDAR protein expression but not NMDAR mRNA expression. Through luciferase reporter assay, we showed that miR-217 could directly bind to the 3′- UTR of NMDAR. MiR-217 mimic transfection also released the inhibition of cAMP-response element-binding protein ( CREB)- PGC-1α signalling induced by homocysteine. Additionally, restoration of PGC-1α expression via Ad PGC-1α infection markedly suppressed VSMCs proliferation through the degradation of NADPH oxidase ( NOX1) and reduction of reactive oxygen species ( ROS). Collectively, our study identified the role of miR-217 in regulating VSMCs proliferation and migration, which might serve as a target for atherosclerosis therapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- HYPERHOMOCYSTEINEMIA
MUSCLE cells
ASPARTIC acid
ATHEROSCLEROSIS
HOMOCYSTEINE
Subjects
Details
- Language :
- English
- ISSN :
- 03051870
- Volume :
- 43
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Pharmacology & Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 117789516
- Full Text :
- https://doi.org/10.1111/1440-1681.12611