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

J. Biol. Chem., Vol. 279, Issue 53, 55675-55681, December 31, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/53/55675    most recent M406532200v1 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 Grote, K. Articles by Schieffer, B. Search for Related Content PubMed PubMed Citation Articles by Grote, K. Articles by Schieffer, B. Social Bookmarking                      What's this?

Stretch-inducible Expression of the Angiogenic Factor CCN1 in Vascular Smooth Muscle Cells Is Mediated by Egr-1^*

Karsten Grote, Udo Bavendiek, Christina Grothusen, Inna Flach, Denise Hilfiker-Kleiner, Helmut Drexler, and Bernhard Schieffer

From the Department of Cardiology and Angiology, Medical School of Hannover, Hannover 30625 Germany

CCN1 is an angiogenic factor that promotes cell adhesion, proliferation, and differentiation. CCN1-deficient mice suffer embryonic death because of vascular defects, demonstrating that CCN1 is required for vessel development. Because mechanical stretch may act as a trigger for vessel development, we investigated the impact of mechanical stretch on the regulatory mechanism of CCN1 expression. Mechanical stretch rapidly enhances CCN1 expression and release in vascular smooth muscle cells (VSMC) in vitro and CCN1 expression in murine aortic segments in vivo. Transfection experiments of VSMC with deletion constructs of the CCN1 promoter revealed the regulatory region responsible for the stretch-induced CCN1 expression in the 200-bp promoter region upstream of the TATA-box containing potential binding sites for early growth response-1 (Egr-1), nuclear factor of activated T-cells and cAMP response element binding protein. Decoy oligonucleotides to Egr-1, but not to nuclear factor of activated T-cells or cAMP response element binding protein, abolished the stretch-induced transcription of CCN1. In addition, mutagenesis of the Egr-1 binding site within the CCN1 promoter completely blunted the stretch-induced activation of the promoter. Furthermore, mechanical stretch induced the expression and DNA-binding activity of Egr-1 in VSMC as demonstrated by Western blot and electromobility shift assay. Moreover, a pressure overload-dependent de novo synthesis of Egr-1 was observed after aortic banding. These findings indicate that mechanical stretch leads to enhanced expression of CCN1 via the mechanosensitive transcription factor Egr-1, suggesting a central role for mechanical stretch in the regulation of CCN1-dependent pro-angiogenic potency.

Received for publication, June 11, 2004 , and in revised form, September 24, 2004.

^* This work was supported by Deutsche Forschungsgemeinschaft Sonderforschungsbereich grant TR02/B4. 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.

To whom correspondence should be addressed: Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Tel.: 49-511-532-8217; Fax: 49-511-532-3263; E-mail: grote.karsten{at}mh-hannover.de.

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

This article has been cited by other articles:

				R. Kivela, H. Kyrolainen, H. Selanne, P. V. Komi, H. Kainulainen, and V. Vihko A single bout of exercise with high mechanical loading induces the expression of Cyr61/CCN1 and CTGF/CCN2 in human skeletal muscle J Appl Physiol, October 1, 2007; 103(4): 1395 - 1401. [Abstract] [Full Text] [PDF]

				G. Matute-Bello, M. M. Wurfel, J. S. Lee, D. R. Park, C. W. Frevert, D. K. Madtes, S. D. Shapiro, and T. R. Martin Essential Role of MMP-12 in Fas-Induced Lung Fibrosis Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 210 - 221. [Abstract] [Full Text] [PDF]

				K. Grote, G. Salguero, M. Ballmaier, M. Dangers, H. Drexler, and B. Schieffer The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration Blood, August 1, 2007; 110(3): 877 - 885. [Abstract] [Full Text] [PDF]

				H.-Y. Lee, J.-W. Chung, S.-W. Youn, J.-Y. Kim, K.-W. Park, B.-K. Koo, B.-H. Oh, Y.-B. Park, B. Chaqour, K. Walsh, et al. Forkhead Transcription Factor FOXO3a Is a Negative Regulator of Angiogenic Immediate Early Gene CYR61, Leading to Inhibition of Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia Circ. Res., February 16, 2007; 100(3): 372 - 380. [Abstract] [Full Text] [PDF]

				L. M. Khachigian Early Growth Response-1 in Cardiovascular Pathobiology Circ. Res., February 3, 2006; 98(2): 186 - 191. [Abstract] [Full Text] [PDF]

				F. Sozo, M. J. Wallace, V. A. Zahra, C. E. Filby, and S. B. Hooper Gene expression profiling during increased fetal lung expansion identifies genes likely to regulate development of the distal airways Physiol Genomics, January 12, 2006; 24(2): 105 - 113. [Abstract] [Full Text] [PDF]