Document Detail


Matrix metalloproteinases modulated by protein kinase Cε mediate resistin-induced migration of human coronary artery smooth muscle cells.
MedLine Citation:
PMID:  21277149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Emerging evidence showed that resistin induces vascular smooth muscle cell (VSMC) migration, a critical step in initiating vascular restenosis. Adhesion molecule expression and cytoskeletal rearrangement have been observed in this progress. Given that matrix metalloproteinases (MMPs) also regulate cell migration, we hypothesized that MMPs may mediate resistin-induced VSMC migration.
METHODS: Human VSMCs were treated with recombinant human resistin at physiologic (10 ng/mL) and pathologic (40 ng/mL) concentrations for 24 hours. Cell migration was determined by the Boyden chamber assay. MMP and tissue inhibitor metalloproteinase (TIMP) mRNA and protein levels were measured with real-time PCR and ELISA. MMP enzymatic activity was measured by zymography. In another experiment, neutralizing antibodies against MMP-2 and MMP-9 were coincubated with resistin in cultured VSMCs. The regulation of MMP by protein kinase C (PKC) was determined by εV1-2, a selective PKCε inhibitor.
RESULTS: Resistin-induced smooth muscle cell (SMC) migration was confirmed by the Boyden chamber assay. Forty nanograms/milliliter resistin increased SMC migration by 3.7 fold. Additionally, resistin stimulated MMP-2 and -MMP9 mRNA and protein expressions. In contrast, the TIMP-1 and TIMP-2 mRNA levels were inhibited by resistin. Neutralizing antibodies against MMP-2 and MMP-9 effectively reversed VSMC migration. Furthermore, resistin activated PKCε, but selective PKCε inhibitor suppressed resistin-induced MMP expression, activity, and cell migration.
CONCLUSIONS: Our study confirmed that resistin increased vascular smooth muscle cell migration in vitro. In terms of mechanism, resistin-stimulated cell migration was associated with increased MMP expression, which was dependent on PKCε activation.
Authors:
Qinxue Ding; Hong Chai; Nausheen Mahmood; Jerry Tsao; Daria Mochly-Rosen; Wei Zhou
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Publication Detail:
Type:  Journal Article     Date:  2011-01-31
Journal Detail:
Title:  Journal of vascular surgery     Volume:  53     ISSN:  1097-6809     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-28     Completed Date:  2011-05-27     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1044-51     Citation Subset:  IM    
Copyright Information:
Published by Mosby, Inc.
Affiliation:
Division of Vascular and Endovascular Surgery, Department of Surgery, Stanford University, Stanford, CA 94304, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Migration Assays
Cell Movement* / drug effects
Cells, Cultured
Coronary Vessels / enzymology
Humans
Matrix Metalloproteinase 2 / genetics,  metabolism*
Matrix Metalloproteinase 9 / genetics,  metabolism
Muscle, Smooth, Vascular / drug effects,  enzymology*
Myocytes, Smooth Muscle / drug effects,  enzymology*
Peptide Fragments / pharmacology
Protein Kinase C-epsilon / antagonists & inhibitors,  metabolism*
Protein Kinase Inhibitors / pharmacology
RNA, Messenger / metabolism
Recombinant Proteins / metabolism
Resistin / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction* / drug effects
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Grant Support
ID/Acronym/Agency:
R01 HL052141/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/Protein Kinase Inhibitors; 0/RETN protein, human; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Resistin; 0/Tissue Inhibitor of Metalloproteinase-1; 0/epsilonV1-2 peptide; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 2.7.11.13/PRKCE protein, human; EC 2.7.11.13/Protein Kinase C-epsilon; EC 3.4.24.24/MMP2 protein, human; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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