A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells

Biological research: BR

Jiyun Lee¹  Hyang-Hee Seo¹  Chang Youn Lee²  Kyu Hee Lim³  Soyeon Lim⁴  Eunhyun Choi⁴  Seahyoung Lee⁴  Ki-Chul Hwang⁴  Sang Woo Kim⁴ 

[1] Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea;Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, South Korea;Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Jeonju, South Korea;Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, South Korea

关键词: Syk kinase inhibitor;    BAY61-3606;    VSMC;    Proliferation;    Migration;   

DOI  :  10.1186/s40659-016-0106-3

学科分类：生物科学（综合）

来源: BioMed Central

【 摘 要 】

Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay. Among 43 initially screened small molecule inhibitors of kinases that have no known anti-proliferative effect on VSMCs, a spleen tyrosine kinase (Syk) inhibitor (BAY61-3606) showed significant anti-proliferative effect on VSMCs. Further experiments indicated that BAY61 attenuated the VSMC proliferation in both concentration- and time-dependent manner, and it also significantly suppressed the migration of VSMCs as assessed by both wound healing assays and transwell assays. Additionally, BAY61 suppressed the sprouting of VSMCs from endothelium-removed aortic rings. The present study identified a Syk kinase inhibitor as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its underlying molecular mechanisms, such as its primary target, and to validate its in vivo efficacy as a therapeutic agent for restenosis and atherosclerosis.

【 授权许可】

CC BY