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Interstitial flow induces MMP-1 expression and vascular SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism.
- Source :
-
American Journal of Physiology: Heart & Circulatory Physiology . Jan2010, Vol. 298 Issue 1, pH127-H135. 9p. 1 Chart, 8 Graphs. - Publication Year :
- 2010
-
Abstract
- The migration of vascular smooth muscle cells (SMCs) and fibroblasts into the intima after vascular injury is a central process in vascular lesion formation. The elevation of transmural interstitial flow is also observed after damage to the vascular endothelium. We have previously shown that interstitial flow upregulates matrix metalloproteinase1 (MMP1) expression, which in turn promotes SMC and fibroblast migration in collagen I gels. In this study, we investigated further the mechanism of flow-induced MMP-1 expression. An ERK1/2 inhibitor PD-98059 completely abolished interstitial flow-induced SMC migration and MMP1 expression. Interstitial flow promoted ERK1/2 phosphorylation, whereas PD-98059 abolished flow-induced activation. Silencing ERK 1/2 completely abolished MMP1 expression and SMC migration. In addition, interstitial flow increased the expression of activator protein-1 transcription factors (c-Jun and c-Fos), whereas PD-98059 attenuated flow-induced expression. Knocking down c-jun completely abolished flow-induced MMP1 expression, whereas silencing c-fos did not affect MMP-1 expression. Taken together, our data indicate that interstitial flow induces MMP-l expression and SMC migration in collagen I gels via an ERK1/2-dependent and c-Jun-mediated mechanism and suggest that interstitial flow, ERK1/2 MAPK, c-Jun, and MMP-1 may play important roles in SMC migration and neointima formation after vascular injury. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636135
- Volume :
- 298
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Heart & Circulatory Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 47379738
- Full Text :
- https://doi.org/10.1152/ajpheart.00732.2009