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

J. Biol. Chem., Vol. 279, Issue 36, 37808-37814, September 3, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/36/37808    most recent M400047200v1 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Marano, R. J. Articles by Rakoczy, P. E. Search for Related Content PubMed PubMed Citation Articles by Marano, R. J. Articles by Rakoczy, P. E. Social Bookmarking                      What's this?

Discovery of a Novel Control Element within the 5'-Untranslated Region of the Vascular Endothelial Growth Factor

REGULATION OF EXPRESSION USING SENSE OLIGONUCLEOTIDES^*

Robert J. Marano, Meliha Brankov, and P. Elizabeth Rakoczy¶

From the Department of Molecular Ophthalmology, Lions Eye Institute and the Centre for Ophthalmology and Visual Science, University of Western Australia, 2 Verdun Street, Nedlands, Western Australia 6009, Australia

The regulation of vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, is controlled primarily through the interactions of control elements located within the 5'- and 3'-untranslated regions, many of which are yet to be described. In this study we examined the 5'-untranslated region of human VEGF for control elements with the aim of regulating expression both in vitro and in vivo using oligonucleotide gene therapy. A potential control element was located, two sense oligonucleotides (S₁ and S₂) were designed based on its sequence, and a third oligonucleotide (S₃) was designed as a control and mapped to the 16 base pairs immediately upstream. Retinal cells cultured in the presence of S₁ and S₂ resulted in a 2-fold increase of VEGF protein and a 1.5-fold increase in mRNA 24 h post-transfection whereas S₃ had no significant effect (p > 0.05) compared with controls. Subsequent reporter gene studies confirmed the necessity of this element for up-regulation by S₁. Further in vivo studies showed that S₁ and S₂ mediated an increase in VEGF protein in a rodent ocular model that resulted in angiogenesis. In addition to providing insight into the regulation of the vascular endothelial growth factor, the use of these oligonucleotides to stimulate vascular growth may prove useful for the treatment of ischemic tissues such as those found in the heart following infarct.

Received for publication, January 5, 2004 , and in revised form, May 14, 2004.

^* Portions of this work were funded by 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.

^¶ To whom correspondence should be addressed. Tel.: 61-9381-0735; Fax: 61-9381-0700; E-mail: robert{at}lei.org.au.

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