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

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 therapeuti...

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Main Authors: Hyang‑Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Eunhyun Choi, Soyeon Lim, Seahyoung Lee, Ki‑Chul Hwang
Format: Article
Language:English
Published: BMC
Series:Biological Research
Subjects:
Online Access:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100403&lng=en&tlng=en
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author Hyang‑Hee Seo
Sang Woo Kim
Chang Youn Lee
Kyu Hee Lim
Jiyun Lee
Eunhyun Choi
Soyeon Lim
Seahyoung Lee
Ki‑Chul Hwang
author_facet Hyang‑Hee Seo
Sang Woo Kim
Chang Youn Lee
Kyu Hee Lim
Jiyun Lee
Eunhyun Choi
Soyeon Lim
Seahyoung Lee
Ki‑Chul Hwang
author_sort Hyang‑Hee Seo
collection DOAJ
description 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.
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spelling doaj.art-2ad23e0de45d43e19fde417dc6293f7e2022-12-22T00:41:55ZengBMCBiological Research0716-976050010.1186/s40659-016-0106-3S0716-97602017000100403A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cellsHyang‑Hee SeoSang Woo KimChang Youn LeeKyu Hee LimJiyun LeeEunhyun ChoiSoyeon LimSeahyoung LeeKi‑Chul HwangAbstract 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.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100403&lng=en&tlng=enSyk kinase inhibitorBAY61-3606 VSMCProliferationMigration
spellingShingle Hyang‑Hee Seo
Sang Woo Kim
Chang Youn Lee
Kyu Hee Lim
Jiyun Lee
Eunhyun Choi
Soyeon Lim
Seahyoung Lee
Ki‑Chul Hwang
A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
Biological Research
Syk kinase inhibitor
BAY61-3606 VSMC
Proliferation
Migration
title A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
title_full A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
title_fullStr A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
title_full_unstemmed A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
title_short A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
title_sort spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
topic Syk kinase inhibitor
BAY61-3606 VSMC
Proliferation
Migration
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100403&lng=en&tlng=en
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