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

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474031.do
DOI
10.1186/s40659-016-0106-3
Title
A spleen tyrosine kinase inhibitor attenuates the proliferation andmigration of vascular smooth muscle cells
Description
This study was supported by grants funded by the Korea Ministry ofScience, ICT and Future Planning (NRF-2015M3A9E6029519, andNFR-2015M3A9E6029407).
abstract
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.
provenance
Made available in Cube on 2018-09-28T10:35:22Z (GMT). No. of bitstreams: 0
language
English
author
Seo, Hyang-Hee
Kim, Sang Woo
Lee, Chang Youn
Lim, Kyu Hee
Lee, Jiyun
Choi, Eunhyun
Lim, Soyeon
Lee, Seahyoung
Hwang, Ki-Chul
orcid
Kim, Sang Woo/0000-0002-3144-4822
accessioned
2018-09-28T10:35:22Z
available
2018-09-28T10:35:22Z
issued
2017
citation
BIOLOGICAL RESEARCH(50)
issn
0716-9760
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474031.do
Funder
과학기술정보통신부
Funding Program
바이오.의료기술개발
Project ID
1711054676
Jurisdiction
Rep.of Korea
Project Name
Development of manufacturing technology for fusion cell therapy product targeting cardiovascular disease by modulating genes responsible for stem cell functions and differentiation
rights
openAccess
subject
Syk kinase inhibitor
BAY61-3606
VSMC
Proliferation
Migration
type
article


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