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Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration.

Publication ,  Journal Article
Jagadeesha, DK; Takapoo, M; Banfi, B; Bhalla, RC; Miller, FJ
Published in: Cardiovasc Res
March 1, 2012

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: The Nox1 NADPH oxidase signals through EGFR to activate MMP-9 and promote the shedding of N-cadherin, thereby contributing to SMC migration.

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Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

March 1, 2012

Volume

93

Issue

3

Start / End Page

406 / 413

Location

England

Related Subject Headings

  • src-Family Kinases
  • Thrombin
  • Reactive Oxygen Species
  • NADPH Oxidase 1
  • NADH, NADPH Oxidoreductases
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Mice, Knockout
  • Mice
  • Matrix Metalloproteinase 9
 

Citation

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Jagadeesha, D. K., Takapoo, M., Banfi, B., Bhalla, R. C., & Miller, F. J. (2012). Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration. Cardiovasc Res, 93(3), 406–413. https://doi.org/10.1093/cvr/cvr308
Jagadeesha, Dammanahalli K., Maysam Takapoo, Botond Banfi, Ramesh C. Bhalla, and Francis J. Miller. “Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration.Cardiovasc Res 93, no. 3 (March 1, 2012): 406–13. https://doi.org/10.1093/cvr/cvr308.
Jagadeesha DK, Takapoo M, Banfi B, Bhalla RC, Miller FJ. Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration. Cardiovasc Res. 2012 Mar 1;93(3):406–13.
Jagadeesha, Dammanahalli K., et al. “Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration.Cardiovasc Res, vol. 93, no. 3, Mar. 2012, pp. 406–13. Pubmed, doi:10.1093/cvr/cvr308.
Jagadeesha DK, Takapoo M, Banfi B, Bhalla RC, Miller FJ. Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration. Cardiovasc Res. 2012 Mar 1;93(3):406–413.
Journal cover image

Published In

Cardiovasc Res

DOI

EISSN

1755-3245

Publication Date

March 1, 2012

Volume

93

Issue

3

Start / End Page

406 / 413

Location

England

Related Subject Headings

  • src-Family Kinases
  • Thrombin
  • Reactive Oxygen Species
  • NADPH Oxidase 1
  • NADH, NADPH Oxidoreductases
  • Myocytes, Smooth Muscle
  • Muscle, Smooth, Vascular
  • Mice, Knockout
  • Mice
  • Matrix Metalloproteinase 9