Back to Search
Start Over
MicroRNA-217 suppresses homocysteine-induced proliferation and migration of vascular smooth muscle cells via N-methyl-D-aspartic acid receptor inhibition.
- Source :
-
Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2016 Oct; Vol. 43 (10), pp. 967-75. - 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 microRNA-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(-4)  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 AdPGC-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.<br /> (© 2016 John Wiley & Sons Australia, Ltd.)
- Subjects :
- Animals
Aorta, Thoracic drug effects
Aorta, Thoracic metabolism
Cell Line
Cell Movement drug effects
Cell Proliferation drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Muscle, Smooth, Vascular drug effects
Rats
Rats, Wistar
Cell Movement physiology
Cell Proliferation physiology
Homocysteine pharmacology
MicroRNAs biosynthesis
Muscle, Smooth, Vascular metabolism
Receptors, N-Methyl-D-Aspartate biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1681
- Volume :
- 43
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Clinical and experimental pharmacology & physiology
- Publication Type :
- Academic Journal
- Accession number :
- 27333430
- Full Text :
- https://doi.org/10.1111/1440-1681.12611