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

J. Biol. Chem., Vol. 279, Issue 7, 5314-5322, February 13, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/7/5314    most recent M308512200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hosking, B. M. Articles by Muscat, G. E. O. Search for Related Content PubMed PubMed Citation Articles by Hosking, B. M. Articles by Muscat, G. E. O. Social Bookmarking                      What's this?

The VCAM-1 Gene That Encodes the Vascular Cell Adhesion Molecule Is a Target of the Sry-related High Mobility Group Box Gene, Sox18^*

Brett M. Hosking, S.-C. Mary Wang, Meredith Downes, Peter Koopman, and George E. O. Muscat

From the Institute for Molecular Bioscience, Queensland Biosciences Precinct, University of Queensland, Brisbane, Queensland 4072, Australia

VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of cross-talk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosislymphedema-telangiectasia disorder.

Received for publication, August 4, 2003 , and in revised form, October 28, 2003.

^* This project was supported by a grant from the National Health and Medical Research Council of Australia. 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.

An Australian Research Council Professorial Research Fellow.

A National Health and Medical Research Council (NHMRC) Principal Research Fellow and to whom correspondence should be addressed. Fax: 61-7-3346-2101; E-mail: g.muscat{at}imb.uq.edu.au.

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

This article has been cited by other articles:

				M. Downes, M. Francois, C. Ferguson, R. G. Parton, and P. Koopman Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation Hum. Mol. Genet., August 1, 2009; 18(15): 2839 - 2850. [Abstract] [Full Text] [PDF]

				B. Hosking, M. Francois, D. Wilhelm, F. Orsenigo, A. Caprini, T. Svingen, D. Tutt, T. Davidson, C. Browne, E. Dejana, et al. Sox7 and Sox17 are strain-specific modifiers of the lymphangiogenic defects caused by Sox18 dysfunction in mice Development, July 15, 2009; 136(14): 2385 - 2391. [Abstract] [Full Text] [PDF]

				P. Brouillard and M. Vikkula Genetic causes of vascular malformations Hum. Mol. Genet., October 15, 2007; 16(R2): R140 - R149. [Abstract] [Full Text] [PDF]

				M. M. Gorska, Q. Liang, S. J. Stafford, N. Goplen, N. Dharajiya, L. Guo, S. Sur, M. Gaestel, and R. Alam MK2 controls the level of negative feedback in the NF-{kappa}B pathway and is essential for vascular permeability and airway inflammation J. Exp. Med., July 9, 2007; 204(7): 1637 - 1652. [Abstract] [Full Text] [PDF]

				T. Matsui, M. Kanai-Azuma, K. Hara, S. Matoba, R. Hiramatsu, H. Kawakami, M. Kurohmaru, P. Koopman, and Y. Kanai Redundant roles of Sox17 and Sox18 in postnatal angiogenesis in mice J. Cell Sci., September 1, 2006; 119(17): 3513 - 3526. [Abstract] [Full Text] [PDF]

				N. Young, C. N. Hahn, A. Poh, C. Dong, D. Wilhelm, J. Olsson, G. E. O. Muscat, P. Parsons, J. R. Gamble, and P. Koopman Effect of disrupted SOX18 transcription factor function on tumor growth, vascularization, and endothelial development. J Natl Cancer Inst, August 2, 2006; 98(15): 1060 - 1067. [Abstract] [Full Text] [PDF]

				M. Garcia-Ramirez, J. Martinez-Gonzalez, J. O. Juan-Babot, C. Rodriguez, and L. Badimon Transcription Factor SOX18 Is Expressed in Human Coronary Atherosclerotic Lesions and Regulates DNA Synthesis and Vascular Cell Growth Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2398 - 2403. [Abstract] [Full Text] [PDF]

				T. Niimi, Y. Hayashi, S. Futaki, and K. Sekiguchi SOX7 and SOX17 Regulate the Parietal Endoderm-specific Enhancer Activity of Mouse Laminin {alpha}1 Gene J. Biol. Chem., September 3, 2004; 279(36): 38055 - 38061. [Abstract] [Full Text] [PDF]