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

This Article Full Text Full Text (PDF) Data Supplement Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Sassa, Y. Articles by Ishibashi, T. Search for Related Content PubMed PubMed Citation Articles by Sassa, Y. Articles by Ishibashi, T. Social Bookmarking                What's this?

Bifunctional Properties of Peroxisome Proliferator-Activated Receptor 1 in KDR Gene Regulation Mediated via Interaction With Both Sp1 and Sp3

¹ Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
² Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
³ Research Division and Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts
⁴ Department of Animal Breeding and Genetics, Graduate School of Agriculture, Kyoto University, Kyoto, Japan
⁵ Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

Vascular endothelial growth factor receptor 2 (KDR) plays a critical role in mediating a variety of vasculogenic and angiogenic processes, including diabetic retinopathy. We previously demonstrated that the promoter activity of the KDR gene in retinal capillary endothelial cells (RCECs) was regulated in part by the relative concentration of positive/negative transcription factors Sp1/Sp3. We also reported that the peroxisome proliferator-activated receptor (PPAR) ligand could inhibit intraocular angiogenesis. In the present study, the role of PPAR1 in KDR gene regulation in RCECs was examined. PPAR1 protein physically interacted with both Sp1 and Sp3. Transactivation and electrophoretic mobility shift assays clearly demonstrated novel findings that PPAR1 increased KDR promoter activity by enhancing the interaction between Sp1, but not Sp3, and KDR promoter region without its ligand in RCECs. The ligand-binding site but not the DNA binding site of PPAR1 enhanced the interaction between Sp1 and KDR promoter region. Conversely, PPAR1 ligand 15-deoxy (12,14)-prostaglandin J2 dose-dependently suppressed the binding of KDR promoter region with both Sp1 and Sp3, resulting an inhibition of KDR gene expression. In conclusion, PPAR1 has bifunctional properties in the regulation of KDR gene expression mediated via interaction with both Sp1 and Sp3.

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

This article has been cited by other articles:

				K. J. Higgins, S. Liu, M. Abdelrahim, K. Yoon, K. Vanderlaag, W. Porter, R. P. Metz, and S. Safe Vascular Endothelial Growth Factor Receptor-2 Expression Is Induced by 17{beta}-Estradiol in ZR-75 Breast Cancer Cells by Estrogen Receptor {alpha}/Sp Proteins Endocrinology, July 1, 2006; 147(7): 3285 - 3295. [Abstract] [Full Text] [PDF]

				T. Deng, S. Shan, P.-P. Li, Z.-F. Shen, X.-P. Lu, J. Cheng, and Z.-Q. Ning Peroxisome Proliferator-Activated Receptor-{gamma} Transcriptionally Up-Regulates Hormone-Sensitive Lipase via the Involvement of Specificity Protein-1 Endocrinology, February 1, 2006; 147(2): 875 - 884. [Abstract] [Full Text] [PDF]

				J. Hong, I. Samudio, S. Liu, M. Abdelrahim, and S. Safe Peroxisome Proliferator-Activated Receptor {gamma}-Dependent Activation of p21 in Panc-28 Pancreatic Cancer Cells Involves Sp1 and Sp4 Proteins Endocrinology, December 1, 2004; 145(12): 5774 - 5785. [Abstract] [Full Text] [PDF]