BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling

Authors

Ming Zhang, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing
Min Yang, Department of Cardiology, Beijing Shijitan Hospital, Capital Medical University, China
Liping Liu, Department of Nephrology, First Hospital of Tsinghua University, Beijing 100016, China
Wayne Bond Lau, Department of Emergency Medicine, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA, 19107, USAFollow
Hai Gao, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing
Mankun Xin, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing
Lixiao Su, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing
Jian Wang, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing
Shujuan Cheng, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing
Qian Fan, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, BeijingFollow
Jinghua Liu, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing

Document Type

Article

Publication Date

2014

Comments

This article is the final published version in Oxidative Medicine and Cellular Longevity

Volume 2014, Article number 294150.

The published version is available at DOI: 10.1155/2014/294150

Copyright © Hindawi

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 Ca²⁺ 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 Ca²⁺ 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. © 2014 Ming Zhang et al.

Recommended Citation

Zhang, Ming; Yang, Min; Liu, Liping; Lau, Wayne Bond; Gao, Hai; Xin, Mankun; Su, Lixiao; Wang, Jian; Cheng, Shujuan; Fan, Qian; and Liu, Jinghua, "BMP-2 overexpression augments vascular smooth muscle cell motility by upregulating myosin Va via Erk signaling" (2014). Department of Emergency Medicine Faculty Papers. Paper 32.
https://jdc.jefferson.edu/emfp/32