BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling.
Publication/Presentation Date
1-1-2014
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.
Volume
2014
First Page
294150
Last Page
294150
ISSN
1942-0994
Published In/Presented At
Zhang, M., Yang, M., Liu, L. P., Lau, W. B., Gao, H., Xin, M. K., Su, L. X., Wang, J., Cheng, S. J., Fan, Q., & Liu, J. H. (2014). BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling. Oxidative medicine and cellular longevity, 2014, 294150. https://doi.org/10.1155/2014/294150
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
24790701
Department(s)
Administration and Leadership
Document Type
Article