Bifunctional Properties of Peroxisome Proliferator-Activated Receptor γ1 in KDR Gene Regulation Mediated via Interaction with Both Sp1 and Sp3

Yukio Sassa, Yasuaki Hata, Lloyd Paul Aiello, Yukio Taniguchi, Kimitoshi Kohno, Tatsuro Ishibashi

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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)γ ligand could inhibit intraocular angiogenesis. In the present study, the role of PPARγ1 in KDR gene regulation in RCECs was examined. PPARγ1 protein physically interacted with both Sp1 and Sp3. Transactivation and electrophoretic mobility shift assays clearly demonstrated novel findings that PPARγ1 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 PPARγ1 enhanced the interaction between Sp1 and KDR promoter region. Conversely, PPARγ1 ligand 15-deoxy A (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, PPARγ1 has bifunctional properties in the regulation of KDR gene expression mediated via interaction with both Sp1 and Sp3.

Original languageEnglish
Pages (from-to)1222-1229
Number of pages8
JournalDiabetes
Volume53
Issue number5
DOIs
Publication statusPublished - May 1 2004

Fingerprint

Peroxisome Proliferator-Activated Receptors
Genetic Promoter Regions
Ligands
Endothelial Cells
Genes
Sp3 Transcription Factor
Binding Sites
Sp1 Transcription Factor
Vascular Endothelial Growth Factor Receptor-2
Gene Expression Regulation
Electrophoretic Mobility Shift Assay
Diabetic Retinopathy
Transcriptional Activation
Gene Expression
DNA
Proteins

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Bifunctional Properties of Peroxisome Proliferator-Activated Receptor γ1 in KDR Gene Regulation Mediated via Interaction with Both Sp1 and Sp3. / Sassa, Yukio; Hata, Yasuaki; Aiello, Lloyd Paul; Taniguchi, Yukio; Kohno, Kimitoshi; Ishibashi, Tatsuro.

In: Diabetes, Vol. 53, No. 5, 01.05.2004, p. 1222-1229.

Research output: Contribution to journalArticle

Sassa, Yukio ; Hata, Yasuaki ; Aiello, Lloyd Paul ; Taniguchi, Yukio ; Kohno, Kimitoshi ; Ishibashi, Tatsuro. / Bifunctional Properties of Peroxisome Proliferator-Activated Receptor γ1 in KDR Gene Regulation Mediated via Interaction with Both Sp1 and Sp3. In: Diabetes. 2004 ; Vol. 53, No. 5. pp. 1222-1229.
@article{7cbb39c27de644afad1897d76d811052,
title = "Bifunctional Properties of Peroxisome Proliferator-Activated Receptor γ1 in KDR Gene Regulation Mediated via Interaction with Both Sp1 and Sp3",
abstract = "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)γ ligand could inhibit intraocular angiogenesis. In the present study, the role of PPARγ1 in KDR gene regulation in RCECs was examined. PPARγ1 protein physically interacted with both Sp1 and Sp3. Transactivation and electrophoretic mobility shift assays clearly demonstrated novel findings that PPARγ1 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 PPARγ1 enhanced the interaction between Sp1 and KDR promoter region. Conversely, PPARγ1 ligand 15-deoxy A (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, PPARγ1 has bifunctional properties in the regulation of KDR gene expression mediated via interaction with both Sp1 and Sp3.",
author = "Yukio Sassa and Yasuaki Hata and Aiello, {Lloyd Paul} and Yukio Taniguchi and Kimitoshi Kohno and Tatsuro Ishibashi",
year = "2004",
month = "5",
day = "1",
doi = "10.2337/diabetes.53.5.1222",
language = "English",
volume = "53",
pages = "1222--1229",
journal = "Diabetes",
issn = "0012-1797",
publisher = "医学出版",
number = "5",

}

TY - JOUR

T1 - Bifunctional Properties of Peroxisome Proliferator-Activated Receptor γ1 in KDR Gene Regulation Mediated via Interaction with Both Sp1 and Sp3

AU - Sassa, Yukio

AU - Hata, Yasuaki

AU - Aiello, Lloyd Paul

AU - Taniguchi, Yukio

AU - Kohno, Kimitoshi

AU - Ishibashi, Tatsuro

PY - 2004/5/1

Y1 - 2004/5/1

N2 - 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)γ ligand could inhibit intraocular angiogenesis. In the present study, the role of PPARγ1 in KDR gene regulation in RCECs was examined. PPARγ1 protein physically interacted with both Sp1 and Sp3. Transactivation and electrophoretic mobility shift assays clearly demonstrated novel findings that PPARγ1 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 PPARγ1 enhanced the interaction between Sp1 and KDR promoter region. Conversely, PPARγ1 ligand 15-deoxy A (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, PPARγ1 has bifunctional properties in the regulation of KDR gene expression mediated via interaction with both Sp1 and Sp3.

AB - 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)γ ligand could inhibit intraocular angiogenesis. In the present study, the role of PPARγ1 in KDR gene regulation in RCECs was examined. PPARγ1 protein physically interacted with both Sp1 and Sp3. Transactivation and electrophoretic mobility shift assays clearly demonstrated novel findings that PPARγ1 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 PPARγ1 enhanced the interaction between Sp1 and KDR promoter region. Conversely, PPARγ1 ligand 15-deoxy A (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, PPARγ1 has bifunctional properties in the regulation of KDR gene expression mediated via interaction with both Sp1 and Sp3.

UR - http://www.scopus.com/inward/record.url?scp=2342597134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342597134&partnerID=8YFLogxK

U2 - 10.2337/diabetes.53.5.1222

DO - 10.2337/diabetes.53.5.1222

M3 - Article

C2 - 15111490

AN - SCOPUS:2342597134

VL - 53

SP - 1222

EP - 1229

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 5

ER -