BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling.
Oxid Med Cell Longev
; 2014: 294150, 2014.
Article
in En
| MEDLINE
| ID: mdl-24790701
ABSTRACT
BACKGROUND:
The disruption of physiologic vascular smooth muscle cell (VSMC) migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated.METHODS:
VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR detected the expression of myosin Va and the phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2). Immunofluorescence analysis revealed myosin Va expression locale. Intracellular Ca(2+) oscillations were recorded.RESULTS:
VSMC migration was augmented in VSMCs overexpressing BMP-2 in a dose-dependent manner. siRNA-mediated knockdown of myosin Va inhibited VSMC motility. Both myosin Va mRNA and protein expression significantly increased after BMP-2 administration and were inhibited by Erk1/2 inhibitor U0126. BMP-2 induced Ca(2+) oscillations, generated largely by a "cytosolic oscillator".CONCLUSION:
BMP-2 significantly increased VSMCs migration and myosin Va expression, via the Erk signaling pathway and intracellular Ca(2+) oscillations. We provide additional insight into the pathophysiology of atherosclerosis, and inhibition of BMP-2-induced myosin Va expression may represent a potential therapeutic strategy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myosin Heavy Chains
/
Mitogen-Activated Protein Kinase 1
/
Myosin Type V
/
Mitogen-Activated Protein Kinase 3
/
Bone Morphogenetic Protein 2
/
Muscle, Smooth, Vascular
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Oxid Med Cell Longev
Journal subject:
METABOLISMO
Year:
2014
Document type:
Article
Affiliation country:
China