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PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway

Platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a potent phospholipid mediator and has been reported to be localized in atherosclerotic plaque. However, its role in the progression of atherosclerosis remains unclear. In the present study, we investigated the role...

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Autores principales: Kim, Yun H., Lee, Seung J., Seo, Kyo W., Bae, Jin U., Park, So Y., Kim, Eun K., Bae, Sun S., Kim, Jae H., Kim, Chi D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770081/
https://www.ncbi.nlm.nih.gov/pubmed/23911909
http://dx.doi.org/10.1194/jlr.M037176
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author Kim, Yun H.
Lee, Seung J.
Seo, Kyo W.
Bae, Jin U.
Park, So Y.
Kim, Eun K.
Bae, Sun S.
Kim, Jae H.
Kim, Chi D.
author_facet Kim, Yun H.
Lee, Seung J.
Seo, Kyo W.
Bae, Jin U.
Park, So Y.
Kim, Eun K.
Bae, Sun S.
Kim, Jae H.
Kim, Chi D.
author_sort Kim, Yun H.
collection PubMed
description Platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a potent phospholipid mediator and has been reported to be localized in atherosclerotic plaque. However, its role in the progression of atherosclerosis remains unclear. In the present study, we investigated the role of PAF in the production of matrix metalloproteinase (MMP) in primary vascular smooth muscle cells (VSMCs). When rat aortic primary VSMCs were stimulated with PAF (1 nmol/l), the expressions of MMP-2 mRNA and protein, but not of MMP-9, were significantly increased, and these upregulations were markedly attenuated by inhibiting extracellular signal-regulated kinases (ERKs) using molecular and pharmacological inhibitors, but not by using inhibitors of p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. Likewise, ERK phosphorylation was markedly enhanced in PAF-stimulated VSMCs, and this was attenuated by WEB2086, but not by EGF receptor inhibitor, demonstrating the specificity of PAF receptor (PAFR) in PAF-induced ERK phosphorylation. In immunofluorescence studies, β-arrestin2 in PAF-stimulated VSMCs colocalized with PAFR and phosphorylated ERK (P-ERK). Coimmunoprecipitation results suggest that β-arrestin2-bound PAFRs existed as a complex with P-ERK. In addition, PAF-induced ERK phosphorylation and MMP-2 production were significantly attenuated by β-arrestin2 depletion. Taken together, the study shows that PAF enhances MMP-2 production in VSMCs via a β-arrestin2-dependent ERK signaling pathway.
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spelling pubmed-37700812013-10-18 PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway Kim, Yun H. Lee, Seung J. Seo, Kyo W. Bae, Jin U. Park, So Y. Kim, Eun K. Bae, Sun S. Kim, Jae H. Kim, Chi D. J Lipid Res Research Articles Platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a potent phospholipid mediator and has been reported to be localized in atherosclerotic plaque. However, its role in the progression of atherosclerosis remains unclear. In the present study, we investigated the role of PAF in the production of matrix metalloproteinase (MMP) in primary vascular smooth muscle cells (VSMCs). When rat aortic primary VSMCs were stimulated with PAF (1 nmol/l), the expressions of MMP-2 mRNA and protein, but not of MMP-9, were significantly increased, and these upregulations were markedly attenuated by inhibiting extracellular signal-regulated kinases (ERKs) using molecular and pharmacological inhibitors, but not by using inhibitors of p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. Likewise, ERK phosphorylation was markedly enhanced in PAF-stimulated VSMCs, and this was attenuated by WEB2086, but not by EGF receptor inhibitor, demonstrating the specificity of PAF receptor (PAFR) in PAF-induced ERK phosphorylation. In immunofluorescence studies, β-arrestin2 in PAF-stimulated VSMCs colocalized with PAFR and phosphorylated ERK (P-ERK). Coimmunoprecipitation results suggest that β-arrestin2-bound PAFRs existed as a complex with P-ERK. In addition, PAF-induced ERK phosphorylation and MMP-2 production were significantly attenuated by β-arrestin2 depletion. Taken together, the study shows that PAF enhances MMP-2 production in VSMCs via a β-arrestin2-dependent ERK signaling pathway. The American Society for Biochemistry and Molecular Biology 2013-10 /pmc/articles/PMC3770081/ /pubmed/23911909 http://dx.doi.org/10.1194/jlr.M037176 Text en Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc. http://creativecommons.org/licenses/by/3.0/ Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles
spellingShingle Research Articles
Kim, Yun H.
Lee, Seung J.
Seo, Kyo W.
Bae, Jin U.
Park, So Y.
Kim, Eun K.
Bae, Sun S.
Kim, Jae H.
Kim, Chi D.
PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway
title PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway
title_full PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway
title_fullStr PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway
title_full_unstemmed PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway
title_short PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway
title_sort paf enhances mmp-2 production in rat aortic vsmcs via a β-arrestin2-dependent erk signaling pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770081/
https://www.ncbi.nlm.nih.gov/pubmed/23911909
http://dx.doi.org/10.1194/jlr.M037176
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