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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Seo,Hyang‑Hee, Kim,Sang Woo, Lee,Chang Youn, Lim,Kyu Hee, Lee,Jiyun, Choi,Eunhyun, Lim,Soyeon, Lee,Seahyoung, Hwang,Ki‑Chul
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2017
Materias:	Syk kinase inhibitor BAY61-3606 VSMC Proliferation Migration
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100403
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:scielo:S0716-97602017000100403
record_format	dspace
spelling	oai:scielo:S0716-976020170001004032017-04-10A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cellsSeo,Hyang‑HeeKim,Sang WooLee,Chang YounLim,Kyu HeeLee,JiyunChoi,EunhyunLim,SoyeonLee,SeahyoungHwang,Ki‑Chul Syk kinase inhibitor BAY61-3606 VSMC Proliferation Migration 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.50 20172017-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100403en10.1186/s40659-016-0106-3
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Syk kinase inhibitor BAY61-3606 VSMC Proliferation Migration
spellingShingle	Syk kinase inhibitor BAY61-3606 VSMC Proliferation Migration Seo,Hyang‑Hee Kim,Sang Woo Lee,Chang Youn Lim,Kyu Hee Lee,Jiyun Choi,Eunhyun Lim,Soyeon Lee,Seahyoung Hwang,Ki‑Chul A spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
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.
author	Seo,Hyang‑Hee Kim,Sang Woo Lee,Chang Youn Lim,Kyu Hee Lee,Jiyun Choi,Eunhyun Lim,Soyeon Lee,Seahyoung Hwang,Ki‑Chul
author_facet	Seo,Hyang‑Hee Kim,Sang Woo Lee,Chang Youn Lim,Kyu Hee Lee,Jiyun Choi,Eunhyun Lim,Soyeon Lee,Seahyoung Hwang,Ki‑Chul
author_sort	Seo,Hyang‑Hee
title	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_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_sort	spleen tyrosine kinase inhibitor attenuates the proliferation and migration of vascular smooth muscle cells
publisher	Sociedad de Biología de Chile
publishDate	2017
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602017000100403
work_keys_str_mv	AT seohyang8209hee aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT kimsangwoo aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT leechangyoun aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT limkyuhee aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT leejiyun aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT choieunhyun aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT limsoyeon aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT leeseahyoung aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT hwangki8209chul aspleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT seohyang8209hee spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT kimsangwoo spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT leechangyoun spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT limkyuhee spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT leejiyun spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT choieunhyun spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT limsoyeon spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT leeseahyoung spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells AT hwangki8209chul spleentyrosinekinaseinhibitorattenuatestheproliferationandmigrationofvascularsmoothmusclecells
_version_	1718441566594400256

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

Ejemplares similares