| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Department of Ophthalmology and the 2 Second Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan.
PURPOSE. Vascular endothelial growth factor (VEGF) is an angiogenic peptide that has been implicated in many retinopathies. Although all trans-retinoic acid (atRA) has long been known as an essential factor in the visual cycle, the role of atRA in the pathogenesis of retinal disease remains elusive. In this study, we investigated the effects of atRA on expression of the VEGF gene in retinoblastoma Y79 cells.
METHODS. Total RNA prepared from Y79 cells, with or without atRA, was subjected to Northern blot analyses. Reporter constructs consisting of the VEGF promoter-luciferase gene were transfected into Y79 cells. Nuclear factors binding to the VEGF promoter were analyzed by electrophoretic mobility shift assays (EMSAs).
RESULTS. The levels of VEGF transcripts were increased by atRA in a time- and dose-dependent manner. Progressive deletion and site-specific mutation analyses indicated that atRA increased VEGF promoter activity through a G+C-rich sequence that was shown to be an Sp1-binding site by supershift assays. EMSAs showed that Sp1 binding was increased by atRA stimulation. Although no measurable change was observed in Sp1 mRNA levels, Western blot analysis showed an increase in Sp1 protein levels in the atRA-treated cells. These data suggest that atRA increases Sp1 protein levels by posttranscriptional mechanisms, and elevated levels of Sp1 protein induce the expression of VEGF at the transcriptional level.
CONCLUSIONS. atRA induced transcription of the VEGF gene through Sp1-binding sites in Y79 cells. Pharmacologic intervention that inhibits the signals elicited by atRA may be effective in treating VEGF-mediated retinopathies.
This article has been cited by other articles:
|
|
 |
|
  A. Iriyama, R. Fujiki, Y. Inoue, H. Takahashi, Y. Tamaki, S. Takezawa, K. Takeyama, W.-D. Jang, S. Kato, and Y. Yanagi A2E, a Pigment of the Lipofuscin of Retinal Pigment Epithelial Cells, Is an Endogenous Ligand for Retinoic Acid Receptor J. Biol. Chem., May 2, 2008; 283(18): 11947 - 11953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Sreekumar, J. Zhou, J. Sohn, C. Spee, S. J. Ryan, B. J. Maurer, R. Kannan, and D. R. Hinton N-(4-hydroxyphenyl) Retinamide Augments Laser-Induced Choroidal Neovascularization in Mice Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 1210 - 1220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saito, A. Sugawara, A. Uruno, M. Kudo, H. Kagechika, Y. Sato, Y. Owada, H. Kondo, M. Sato, M. Kurabayashi, et al. All-trans Retinoic Acid Induces in Vitro Angiogenesis via Retinoic Acid Receptor: Possible Involvement of Paracrine Effects of Endogenous Vascular Endothelial Growth Factor Signaling Endocrinology, March 1, 2007; 148(3): 1412 - 1423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Tezel, L. Geng, H. J. Kaplan, and L. V. Del Priore Retinal Pigment Epithelium Rescues Vascular Endothelium from Retinoic Acid-Induced Apoptosis Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5075 - 5087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kobrossy, M. Rastegar, and M. Featherstone Interplay between Chromatin and Trans-acting Factors Regulating the Hoxd4 Promoter during Neural Differentiation J. Biol. Chem., September 8, 2006; 281(36): 25926 - 25939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Akiyama, T. Tanaka, H. Doi, H. Kanai, T. Maeno, H. Itakura, T. Iida, Y. Kimura, S. Kishi, and M. Kurabayashi Visible light exposure induces VEGF gene expression through activation of retinoic acid receptor-{alpha} in retinoblastoma Y79 cells Am J Physiol Cell Physiol, April 1, 2005; 288(4): C913 - C920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pages and J. Pouyssegur Transcriptional regulation of the Vascular Endothelial Growth Factor gene-a concert of activating factors Cardiovasc Res, February 15, 2005; 65(3): 564 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Wolf, R. L. Medcalf, and C. Jern The t-PA -7351C>T enhancer polymorphism decreases Sp1 and Sp3 protein binding affinity and transcriptional responsiveness to retinoic acid Blood, February 1, 2005; 105(3): 1060 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Kairaitis, Y. Wang, M. Gassmann, Y.-C. Tay, and D. C. H. Harris HIF-1{alpha} expression follows microvascular loss in advanced murine adriamycin nephrosis Am J Physiol Renal Physiol, January 1, 2005; 288(1): F198 - F206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sato, T. Tanaka, K. Maemura, T. Uchiyama, H. Sato, T. Maeno, T. Suga, T. Iso, Y. Ohyama, M. Arai, et al. The PAI-1 Gene as a Direct Target of Endothelial PAS Domain Protein-1 in Adenocarcinoma A549 Cells Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 209 - 215. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
