Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor

  • Authors:
    • Mitsuhide Maeda
    • Seiya Kato
    • Shintro Fukushima
    • Utako Kaneyuki
    • Teruhiko Fujii
    • Marcelo G. Kazanietz
    • Koichi Oshima
    • Minoru Shigemori
  • View Affiliations

  • Published online on: April 1, 2006     https://doi.org/10.3892/ijmm.17.4.559
  • Pages: 559-566
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Abstract

The proliferation and migration of vascular smooth muscle cells (SMC) are important aspects of atherogenesis. Activated growth factor signaling in injured vessels subsequently promotes a number of intracellular events resulting in the phenotypic modulation of SMC. Here, we investigated the role of β2-chimaerin, a non-protein kinase C phorbol ester receptor with Rac-GTPase-activating protein activity, in growth factor-stimulated SMC. The endogenous expression of β2-chimaerin was detected in cultured human SMC by reverse transcription-polymerase chain reaction and immunohistochemistry. Next, the overexpression of HA-tagged wild-type human β2-chimaerin was attempted using cultured rat SMC with a recombinant adenovirus (Adv-β2-Chim). Adv-LZ encoding β-galactosidase (LacZ) was used as the control. The proliferation of SMC stimulated by platelet-derived growth factor (PDGF-BB, 10 ng/ml), as measured by cell-counting and 5-bromo-2'deoxyuridine incorporation assay, was suppressed by infection with Adv-β2-Chim (50-200 MOI), but not with control viruses. PDGF-induced SMC migration was inhibited by approximately 25% after infection with Adv-β2-Chim (200 MOI) using a modified Boyden's chamber assay with a fibronectin-coated membrane. Confocal microscopy revealed that PDGF stimulation altered the sub-cellular localization of β2-chimaerin. The administration of 12-O-tetradecanoyl phorbol 13-acetate also induced changes in the sub-cellular localization of β2-chimaerin, which was not affected by a presence of the PKC inhibitor (GF109203X). Finally, PDGF-induced Rac1 activation was found to be inhibited in the Adv-β2-Chim-infected cells. Thus, we demonstrated that β2-chimaerin regulates the proliferation and migration of SMC downstream of growth factor signaling pathway via the regulation of Rac1 activity. The signaling mediated by β2-chimaerin may play a role in the regulation of SMC phenotypes, thereby implicating human atherogenesis.

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April 2006
Volume 17 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Maeda M, Kato S, Fukushima S, Kaneyuki U, Fujii T, Kazanietz MG, Oshima K and Shigemori M: Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor. Int J Mol Med 17: 559-566, 2006.
APA
Maeda, M., Kato, S., Fukushima, S., Kaneyuki, U., Fujii, T., Kazanietz, M.G. ... Shigemori, M. (2006). Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor. International Journal of Molecular Medicine, 17, 559-566. https://doi.org/10.3892/ijmm.17.4.559
MLA
Maeda, M., Kato, S., Fukushima, S., Kaneyuki, U., Fujii, T., Kazanietz, M. G., Oshima, K., Shigemori, M."Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor". International Journal of Molecular Medicine 17.4 (2006): 559-566.
Chicago
Maeda, M., Kato, S., Fukushima, S., Kaneyuki, U., Fujii, T., Kazanietz, M. G., Oshima, K., Shigemori, M."Regulation of vascular smooth muscle proliferation and migration by β2-chimaerin, a non-protein kinase C phorbol ester receptor". International Journal of Molecular Medicine 17, no. 4 (2006): 559-566. https://doi.org/10.3892/ijmm.17.4.559