RGD Reference Report - PAF enhances MMP-2 production in rat aortic VSMCs via a beta-arrestin2-dependent ERK signaling pathway. - Rat Genome Database

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

Authors: Kim, YH  Lee, SJ  Seo, KW  Bae, JU  Park, SY  Kim, EK  Bae, SS  Kim, JH  Kim, CD 
Citation: Kim YH, etal., J Lipid Res. 2013 Oct;54(10):2678-86. doi: 10.1194/jlr.M037176. Epub 2013 Aug 2.
RGD ID: 8657085
Pubmed: PMID:23911909   (View Abstract at PubMed)
PMCID: PMC3770081   (View Article at PubMed Central)
DOI: DOI:10.1194/jlr.M037176   (Journal Full-text)

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, beta-arrestin2 in PAF-stimulated VSMCs colocalized with PAFR and phosphorylated ERK (P-ERK). Coimmunoprecipitation results suggest that beta-arrestin2-bound PAFRs existed as a complex with P-ERK. In addition, PAF-induced ERK phosphorylation and MMP-2 production were significantly attenuated by beta-arrestin2 depletion. Taken together, the study shows that PAF enhances MMP-2 production in VSMCs via a beta-arrestin2-dependent ERK signaling pathway.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellular space  IDA 8657085 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Arrb2  (arrestin, beta 2)
Mmp2  (matrix metallopeptidase 2)
Ptafr  (platelet-activating factor receptor)


Additional Information