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

Autor: Jin Ung Bae, So Youn Park, Kyo Won Seo, Eun Kyoung Kim, Sun Sik Bae, Seung Jin Lee, Jae Ho Kim, Chi Dae Kim, Yun Hak Kim
Rok vydání: 2013
Předmět:
Male
platelet-activating factor
medicine.medical_specialty
Vascular smooth muscle
Arrestins
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
Myocytes
Smooth Muscle
QD415-436
Platelet Membrane Glycoproteins
Biology
matrix metalloproteinase-2
Biochemistry
Muscle
Smooth
Vascular
Receptors
G-Protein-Coupled
Rats
Sprague-Dawley
chemistry.chemical_compound
Endocrinology
Internal medicine
medicine
Animals
Phosphorylation
Platelet Activating Factor
Protein kinase A
Receptor
Extracellular Signal-Regulated MAP Kinases
extracellular signal-regulated kinase
Aorta
Cells
Cultured
beta-Arrestins
Research Articles
β-arrestin2
Platelet-activating factor
Kinase
platelet-activating factor receptor
Cell Biology
Cell biology
Rats
Protein Transport
chemistry
Enzyme Induction
Matrix Metalloproteinase 2
lipids (amino acids
peptides
and proteins)
Platelet-activating factor receptor
Protein Processing
Post-Translational
Zdroj: Journal of Lipid Research
Journal of Lipid Research, Vol 54, Iss 10, Pp 2678-2686 (2013)
ISSN: 1539-7262
Popis: 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.
Databáze: OpenAIRE
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