Journal article
Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration
Cardiovascular research, Vol.93(3), pp.406-413
03/01/2012
DOI: 10.1093/cvr/cvr308
PMCID: PMC3282575
PMID: 22102727
Abstract
In atherosclerosis and restenosis, vascular smooth muscle cells (SMCs) migrate into the subendothelial space and proliferate, contributing to neointimal formation. The goal of this study was to define the signalling pathway by which Nox1 NAPDH oxidase mediates SMC migration.
SMCs were cultured from thoracic aorta from Nox1(/y) (Nox1 knockout, KO) and wild-type (WT) mice. In response to thrombin, WT but not Nox1 KO SMCs generated increased levels of reactive oxygen species (ROS). Deficiency of Nox1 prevented thrombin-induced phosphorylation of Src and the subsequent transactivation of the epidermal growth factor receptor (EGFR) at multiple tyrosine residues. Next, activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and matrix metalloproteinase-9 (MMP-9) by thrombin was inhibited by the EGFR inhibitor AG1478 and in Nox1 KO SMCs. Thrombin-induced shedding of N-cadherin from the plasma membrane was dependent on the presence of Nox1 and was blocked by AG1478 and an inhibitor of metalloproteinases. Migration of SMCs to thrombin was impaired in the Nox1 KO SMCs and was restored by expression of Nox1. Finally, treatment of WT SMCs with AG1478 abrogated Nox1-dependent SMC migration.
The Nox1 NADPH oxidase signals through EGFR to activate MMP-9 and promote the shedding of N-cadherin, thereby contributing to SMC migration.
Details
- Title: Subtitle
- Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration
- Creators
- Dammanahalli K. Jagadeesha - University of IowaMaysam Takapoo - Veterans Health AdministrationBotond Banfi - Department of Anatomy and Cell Biology, andRamesh C. Bhalla - Department of Anatomy and Cell Biology, andFrancis J. Miller - Department of Anatomy and Cell Biology, and
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.93(3), pp.406-413
- Publisher
- Oxford Univ Press
- DOI
- 10.1093/cvr/cvr308
- PMID
- 22102727
- PMCID
- PMC3282575
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Number of pages
- 8
- Grant note
- Office of Research and Development, Department of Veterans Affairs; US Department of Veterans Affairs P30DK054759 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P30 DK 54759 / NIH/NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) HL081750; HL14388 / National Heart, Lung, and Blood Institute at the National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01HL081750 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 03/01/2012
- Academic Unit
- Anatomy and Cell Biology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984288641502771
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