HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 7, 4448-4458, February 15, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/7/4448    most recent M709051200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Vigetti, D. Articles by Passi, A. PubMed PubMed Citation Articles by Vigetti, D. Articles by Passi, A. Social Bookmarking                      What's this?

Hyaluronan-CD44-ERK1/2 Regulate Human Aortic Smooth Muscle Cell Motility during Aging^*

Davide Vigetti, Manuela Viola, Eugenia Karousou, Manuela Rizzi, Paola Moretto, Anna Genasetti, Moira Clerici, Vincent C. Hascall, Giancarlo De Luca¹, and Alberto Passi¹

From the Dip. di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy and the Department of Biomedical Engineering and Orthopaedic Research Center/ND20, The Cleveland Clinic Foundation, Cleveland, Ohio 44195

The glycosaminoglycan hyaluronan (HA) modulates cell proliferation and migration, and it is involved in several human vascular pathologies including atherosclerosis and vascular restenosis. During intima layer thickening, HA increases dramatically in the neointima extracellular matrix. Aging is one of the major risk factors for the insurgence of vascular diseases, in which smooth muscle cells (SMCs) play a role by determining neointima formation through their migration and proliferation. Therefore, we established an in vitro aging model consisting of sequential passages of human aortic smooth muscle cells (AoSMCs). Comparing young and aged cells, we found that, during the aging process in vitro,HA synthesis significantly increases, as do HA synthetic enzymes (i.e. HAS2 and HAS3), the precursor synthetic enzyme (UDP-glucose dehydrogenase), and the HA receptor CD44. In aged cells, we also observed increased CD44 signaling that consisted of higher levels of phosphorylated MAP kinase ERK1/2. Further, aged AoSMCs migrated faster than young cells, and such migration could be modulated by HA, which alters the ERK1/2 phosphorylation. HA oligosaccharides of 6.8 kDa and an anti-CD44 blocking antibody prevented ERK1/2 phosphorylation and inhibited AoSMCs migration. These results indicate that, during aging, HA can modulate cell migration involving CD44-mediated signaling through ERK1/2. These data suggest that age-related HA accumulation could promote SMC migration and intima thickening during vascular neointima formation.

Received for publication, November 5, 2007 , and in revised form, December 12, 2007.

^* This work was supported by Ministero dell'Università e della Ricerca (PRIN) (to D. V.), University of Insubria (FAR) (to D. V., A. P., M. V., and G. D. L.), and by Centro Interuniversitario di Biotecnologie (CIB) (to A. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, via J. H. Dunant 5, 21100 Varese, Italy. Tel.: 39-0332-217142; Fax: 39-0332-217119; E-mail: alberto.passi{at}uninsubria.it.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?