Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell migration via ROCK and ERK/p38 MAPK pathways

Matrix metalloproteinases (MMP) play a pivotal role in the pathogenesis of cardiovascular diseases. Their expressions are altered in response to a variety of stimuli, including growth factors, inflammatory markers, and cytokines. In this study, we demonstrated that platelet-derived growth factor-BB...

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Veröffentlicht in:Molecular and cellular biochemistry 2014-08, Vol.393 (1-2), p.255-263
Hauptverfasser: Cui, Ying, Sun, Yin-Wei, Lin, Hai-Shuang, Su, Wei-Min, Fang, Yan, Zhao, Ying, Wei, Xiao-Qing, Qin, Yuan-Hua, Kohama, Kazuhiro, Gao, Ying
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container_title Molecular and cellular biochemistry
container_volume 393
creator Cui, Ying
Sun, Yin-Wei
Lin, Hai-Shuang
Su, Wei-Min
Fang, Yan
Zhao, Ying
Wei, Xiao-Qing
Qin, Yuan-Hua
Kohama, Kazuhiro
Gao, Ying
description Matrix metalloproteinases (MMP) play a pivotal role in the pathogenesis of cardiovascular diseases. Their expressions are altered in response to a variety of stimuli, including growth factors, inflammatory markers, and cytokines. In this study, we demonstrated that platelet-derived growth factor-BB (PDGF-BB) induces a dose- and time-dependent increase in MMP-2 expression in rat vascular smooth muscle cells (VSMC). Treatment with either the Rho-associated protein kinase (ROCK) inhibitor Y-27632 or suppression of ROCK-1/2 by small interfering RNA technology significantly reduced the MMP-2 expression, thus suggesting that ROCK regulates such expression. Similar results were observed when VSMC were pretreated with either U0126 or SB203580, which are selective inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, respectively, thus suggesting that these kinases are important for the induction of MMP-2 expression by PDGF-BB. In conclusion, these results described a novel mechanism in atherosclerosis through PDGF-BB signaling in VSMC, in which MMP-2 expression is induced via extracellular signal-regulated kinases and p38 mitogen-activated protein kinase phosphorylation, as well as ROCK.
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Their expressions are altered in response to a variety of stimuli, including growth factors, inflammatory markers, and cytokines. In this study, we demonstrated that platelet-derived growth factor-BB (PDGF-BB) induces a dose- and time-dependent increase in MMP-2 expression in rat vascular smooth muscle cells (VSMC). Treatment with either the Rho-associated protein kinase (ROCK) inhibitor Y-27632 or suppression of ROCK-1/2 by small interfering RNA technology significantly reduced the MMP-2 expression, thus suggesting that ROCK regulates such expression. Similar results were observed when VSMC were pretreated with either U0126 or SB203580, which are selective inhibitors of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, respectively, thus suggesting that these kinases are important for the induction of MMP-2 expression by PDGF-BB. In conclusion, these results described a novel mechanism in atherosclerosis through PDGF-BB signaling in VSMC, in which MMP-2 expression is induced via extracellular signal-regulated kinases and p38 mitogen-activated protein kinase phosphorylation, as well as ROCK.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-014-2068-5</identifier><identifier>PMID: 24792035</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject><![CDATA[Amides - administration & dosage ; Animals ; Aorta - cytology ; Aorta - metabolism ; Atherosclerosis ; Atherosclerosis - etiology ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Biochemistry ; Biomedical and Life Sciences ; Butadienes - administration & dosage ; Cardiology ; Cardiovascular diseases ; Cell adhesion & migration ; Cell Line ; Cell Movement - drug effects ; Cytokines ; Gene Expression Regulation - drug effects ; Growth factors ; Humans ; Imidazoles - administration & dosage ; Life Sciences ; Matrix Metalloproteinase 2 - biosynthesis ; Matrix Metalloproteinase 2 - metabolism ; Medical Biochemistry ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - metabolism ; Nitriles - administration & dosage ; Oncology ; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phosphotransferases ; Platelet-derived growth factor ; Protein expression ; Proto-Oncogene Proteins c-sis - administration & dosage ; Proto-Oncogene Proteins c-sis - metabolism ; Pyridines - administration & dosage ; Rats ; rho-Associated Kinases - antagonists & inhibitors ; rho-Associated Kinases - metabolism ; RNA ; Rocks ; Rodents ; Signal transduction ; Smooth muscle]]></subject><ispartof>Molecular and cellular biochemistry, 2014-08, Vol.393 (1-2), p.255-263</ispartof><rights>Springer Science+Business Media New York 2014</rights><rights>COPYRIGHT 2014 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-35af43dd4eee3fe8fafc5bb15004f3d0b0c49c27675725dccadd8ae5cee60c4d3</citedby><cites>FETCH-LOGICAL-c538t-35af43dd4eee3fe8fafc5bb15004f3d0b0c49c27675725dccadd8ae5cee60c4d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-014-2068-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-014-2068-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24792035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cui, Ying</creatorcontrib><creatorcontrib>Sun, Yin-Wei</creatorcontrib><creatorcontrib>Lin, Hai-Shuang</creatorcontrib><creatorcontrib>Su, Wei-Min</creatorcontrib><creatorcontrib>Fang, Yan</creatorcontrib><creatorcontrib>Zhao, Ying</creatorcontrib><creatorcontrib>Wei, Xiao-Qing</creatorcontrib><creatorcontrib>Qin, Yuan-Hua</creatorcontrib><creatorcontrib>Kohama, Kazuhiro</creatorcontrib><creatorcontrib>Gao, Ying</creatorcontrib><title>Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell migration via ROCK and ERK/p38 MAPK pathways</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>Matrix metalloproteinases (MMP) play a pivotal role in the pathogenesis of cardiovascular diseases. 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subjects Amides - administration & dosage
Animals
Aorta - cytology
Aorta - metabolism
Atherosclerosis
Atherosclerosis - etiology
Atherosclerosis - metabolism
Atherosclerosis - pathology
Biochemistry
Biomedical and Life Sciences
Butadienes - administration & dosage
Cardiology
Cardiovascular diseases
Cell adhesion & migration
Cell Line
Cell Movement - drug effects
Cytokines
Gene Expression Regulation - drug effects
Growth factors
Humans
Imidazoles - administration & dosage
Life Sciences
Matrix Metalloproteinase 2 - biosynthesis
Matrix Metalloproteinase 2 - metabolism
Medical Biochemistry
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - metabolism
Nitriles - administration & dosage
Oncology
p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases - metabolism
Phosphotransferases
Platelet-derived growth factor
Protein expression
Proto-Oncogene Proteins c-sis - administration & dosage
Proto-Oncogene Proteins c-sis - metabolism
Pyridines - administration & dosage
Rats
rho-Associated Kinases - antagonists & inhibitors
rho-Associated Kinases - metabolism
RNA
Rocks
Rodents
Signal transduction
Smooth muscle
title Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell migration via ROCK and ERK/p38 MAPK pathways
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