Mechanical Stretch Increases MMP-2 Production in Vascular Smooth MuscleCells via Activation of PDGFR-beta/Akt Signaling Pathway
| Autor: | Seung Jin Lee, Kyo Won Seo, So Youn Park, Yun Hak Kim, Sun Sik Bae, Jin Ung Bae, Chi Dae Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Vascular smooth muscle
Anatomy and Physiology Valvular Disease Gene Expression Cardiovascular Cardiovascular System Receptor tyrosine kinase Muscle Smooth Vascular Rats Sprague-Dawley Molecular Cell Biology Cell Mechanics Biomechanics Membrane Receptor Signaling Phosphorylation Musculoskeletal System Cells Cultured Multidisciplinary Microscopy Confocal biology Reverse Transcriptase Polymerase Chain Reaction Tyrphostins musculoskeletal system Immunohistochemistry Signaling Cascades Cell biology Hypertension cardiovascular system Matrix Metalloproteinase 2 Medicine RNA Interference Signal transduction tissues Platelet-derived growth factor receptor Research Article Signal Transduction Tissue Mechanics Science Immunoblotting Myocytes Smooth Muscle Receptor Platelet-Derived Growth Factor beta Vascular Biology Akt Signaling Cascade Animals Protein kinase B Biology PI3K/AKT/mTOR pathway Akt/PKB signaling pathway Molecular biology Rats biology.protein Stress Mechanical Reactive Oxygen Species Proto-Oncogene Proteins c-akt |
| Zdroj: | PLOS ONE(8): 8 PLoS ONE, Vol 8, Iss 8, p e70437 (2013) PLoS ONE |
| Popis: | Increased blood pressure, leading to mechanical stress on vascular smooth muscle cells (VSMC), is a known risk factor for vascular remodeling via increased activity of matrix metalloproteinase (MMP) within the vascular wall. This study aimed to identify cell surface mechanoreceptors and intracellular signaling pathways that influence VSMC to produce MMP in response to mechanical stretch (MS). When VSMC was stimulated with MS (0-10% strain, 60 cycles/min), both production and gelatinolytic activity of MMP-2, but not MMP-9, were increased in a force-dependent manner. MS-enhanced MMP-2 expression and activity were inhibited by molecular inhibition of Akt using Akt siRNA as well as by PI3K/Akt inhibitors, LY293002 and AI, but not by MAPK inhibitors such as PD98059, SP600125 and SB203580. MS also increased Akt phosphorylation in VSMC, which was attenuated by AG1295, a PDGF receptor (PDGFR) inhibitor, but not by inhibitors for other receptor tyrosine kinase including EGF, IGF, and FGF receptors. Although MS activated PDGFR-alpha as well as PDGFR-beta in VSMC, MS-induced Akt phosphorylation was inhibited by molecular deletion of PDGFR-beta using siRNA, but not by inhibition of PDGFR-alpha. Collectively, our data indicate that MS induces MMP-2 production in VSMC via activation of Akt pathway, that is mediated by activation of PDGFR-beta signaling pathways. |
| Databáze: | OpenAIRE |
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