Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.

Increased blood pressure, leading to mechanical stress on vascular smooth muscle cells (VSMC), is a known risk factor for vascular remodeling via increased activity of matrix metalloproteinase (MMP) within the vascular wall. This study aimed to identify cell surface mechanoreceptors and intracellula...

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Autores principales:	Kyo Won Seo, Seung Jin Lee, Yun Hak Kim, Jin Ung Bae, So Youn Park, Sun Sik Bae, Chi Dae Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df3623cf4e674715856fa5bbcaed8173
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spelling	oai:doaj.org-article:df3623cf4e674715856fa5bbcaed81732021-11-18T09:00:48ZMechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.1932-620310.1371/journal.pone.0070437https://doaj.org/article/df3623cf4e674715856fa5bbcaed81732013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23950935/?tool=EBIhttps://doaj.org/toc/1932-6203Increased blood pressure, leading to mechanical stress on vascular smooth muscle cells (VSMC), is a known risk factor for vascular remodeling via increased activity of matrix metalloproteinase (MMP) within the vascular wall. This study aimed to identify cell surface mechanoreceptors and intracellular signaling pathways that influence VSMC to produce MMP in response to mechanical stretch (MS). When VSMC was stimulated with MS (0-10% strain, 60 cycles/min), both production and gelatinolytic activity of MMP-2, but not MMP-9, were increased in a force-dependent manner. MS-enhanced MMP-2 expression and activity were inhibited by molecular inhibition of Akt using Akt siRNA as well as by PI3K/Akt inhibitors, LY293002 and AI, but not by MAPK inhibitors such as PD98059, SP600125 and SB203580. MS also increased Akt phosphorylation in VSMC, which was attenuated by AG1295, a PDGF receptor (PDGFR) inhibitor, but not by inhibitors for other receptor tyrosine kinase including EGF, IGF, and FGF receptors. Although MS activated PDGFR-α as well as PDGFR-β in VSMC, MS-induced Akt phosphorylation was inhibited by molecular deletion of PDGFR-β using siRNA, but not by inhibition of PDGFR-α. Collectively, our data indicate that MS induces MMP-2 production in VSMC via activation of Akt pathway, that is mediated by activation of PDGFR-β signaling pathways.Kyo Won SeoSeung Jin LeeYun Hak KimJin Ung BaeSo Youn ParkSun Sik BaeChi Dae KimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70437 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyo Won Seo Seung Jin Lee Yun Hak Kim Jin Ung Bae So Youn Park Sun Sik Bae Chi Dae Kim Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.
description	Increased blood pressure, leading to mechanical stress on vascular smooth muscle cells (VSMC), is a known risk factor for vascular remodeling via increased activity of matrix metalloproteinase (MMP) within the vascular wall. This study aimed to identify cell surface mechanoreceptors and intracellular signaling pathways that influence VSMC to produce MMP in response to mechanical stretch (MS). When VSMC was stimulated with MS (0-10% strain, 60 cycles/min), both production and gelatinolytic activity of MMP-2, but not MMP-9, were increased in a force-dependent manner. MS-enhanced MMP-2 expression and activity were inhibited by molecular inhibition of Akt using Akt siRNA as well as by PI3K/Akt inhibitors, LY293002 and AI, but not by MAPK inhibitors such as PD98059, SP600125 and SB203580. MS also increased Akt phosphorylation in VSMC, which was attenuated by AG1295, a PDGF receptor (PDGFR) inhibitor, but not by inhibitors for other receptor tyrosine kinase including EGF, IGF, and FGF receptors. Although MS activated PDGFR-α as well as PDGFR-β in VSMC, MS-induced Akt phosphorylation was inhibited by molecular deletion of PDGFR-β using siRNA, but not by inhibition of PDGFR-α. Collectively, our data indicate that MS induces MMP-2 production in VSMC via activation of Akt pathway, that is mediated by activation of PDGFR-β signaling pathways.
format	article
author	Kyo Won Seo Seung Jin Lee Yun Hak Kim Jin Ung Bae So Youn Park Sun Sik Bae Chi Dae Kim
author_facet	Kyo Won Seo Seung Jin Lee Yun Hak Kim Jin Ung Bae So Youn Park Sun Sik Bae Chi Dae Kim
author_sort	Kyo Won Seo
title	Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.
title_short	Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.
title_full	Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.
title_fullStr	Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.
title_full_unstemmed	Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.
title_sort	mechanical stretch increases mmp-2 production in vascular smooth muscle cells via activation of pdgfr-β/akt signaling pathway.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/df3623cf4e674715856fa5bbcaed8173
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Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.

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