11 34

Cited 0 times in

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

 Hyang-Hee Seo  ;  Sang Woo Kim  ;  Chang Youn Lee  ;  Kyu Hee Lim  ;  Jiyun Lee  ;  Eunhyun Choi  ;  Soyeon Lim  ;  Seahyoung Lee  ;  Ki-Chul Hwang 
 BIOLOGICAL RESEARCH, Vol.50(1) : 1, 2017-01 
Journal Title
Issue Date
Animals ; Aorta, Thoracic / drug effects ; Blotting, Western ; Cell Migration Assays ; Cell Movement / drug effects* ; Cell Proliferation / drug effects* ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Muscle, Smooth, Vascular / cytology ; Muscle, Smooth, Vascular / drug effects* ; Myocytes, Smooth Muscle / drug effects* ; Niacinamide / analogs & derivatives* ; Niacinamide / pharmacology ; Pyrimidines / pharmacology* ; Rats, Sprague-Dawley ; Reproducibility of Results ; Syk Kinase / antagonists & inhibitors* ; Time Factors ; Wound Healing / drug effects
BAY61-3606 ; Migration ; Proliferation ; Syk kinase inhibitor ; VSMC
Background: 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.

Results: 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.

Conclusion: 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.
Files in This Item:
T992017216.pdf Download
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.