PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3β/GATA-6 signaling pathways in TNF-α-activated human endothelial cells

被引：78

作者：

Tsoyi, Konstantin ^{[1
,2
]}

Jang, Hwa Jin ^{[1
,2
]}

Nizamutdinova, Irina Tsoy ^{[3
]}

Park, Kyungok ^{[4
]}

Kim, Young Min ^{[1
]}

Kim, Hye Jung ^{[1
,2
]}

Seo, Han Geuk ^{[1
,2
]}

Lee, Jae Heun ^{[1
,2
]}

Chang, Ki Churl ^{[1
,2
]}

机构：

[1] Gyeongsang Natl Univ, Dept Pharmacol, Inst Hlth Sci, Sch Med, Jinju 660751, South Korea

[2] Gyeongsang Natl Univ, Biomed Ctr BK21, Jinju 660751, South Korea

[3] Texas A&M Univ Syst Hlth Sci Ctr, Cardiovasc Res Inst, Coll Med, Temple, TX 76504 USA

[4] Samsung Elect, HRD Ctr, Samsung Adv Technol Training Inst, Suwon 443822, South Korea

来源：

ATHEROSCLEROSIS | 2010年 / 213卷 / 01期

关键词：

Adhesion molecules; Tumor necrosis factor-alpha; PTEN; Endothelial cells; GATA; Atherosclerosis; NF-KAPPA-B; ADHESION MOLECULE-1 EXPRESSION; GATA TRANSCRIPTION FACTORS; NECROSIS-FACTOR-ALPHA; ATHEROSCLEROSIS; INHIBITOR; INDUCTION; KINASE; ACETYLATION; RECEPTOR-1;

D O I：

10.1016/j.atherosclerosis.2010.07.061

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Phosphotase and tensin homolog deleted on chromosome 10 (PTEN) is a potent negative regulator of PI3K/Akt pathway. Here, we tried to elucidate the role of PTEN in the regulation of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1, induced by TNF-alpha in human endothelial cells (ECs). Transfection with PTEN overexpressing vector resulted in the significant decrease in phosphorylation of Akt in TNF-alpha-treated ECs. PTEN strongly inhibited VCAM-1 but not ICAM-1, however this inhibitory effect was reversed by co-trasfection with constitutively active-Akt (CA-Akt-HA) in TNF-alpha-stimulated ECs. Additionally, silencing of PTEN with specific siRNA showed significant increase of phosphor-Akt compared with TNF-alpha alone treated ECs. siPTEN significantly upregulated VCAM-1 but was indifferent to ICAM-1 in TNF-alpha-treated cells. Further, chromatin immunoprecipitation (ChIP) assay showed that PTEN targets GATA-6 but not IRF-1 binding to VCAM-1 promoter. In addition, GATA-6 is associated with glycogen synthesis kinase-3beta (GSK-3 beta) which is in turn regulated by PTEN-dependent Akt activity. Finally, PTEN significantly prevented monocyte adhesion to TNF-alpha-induced ECs probably through VCAM-1 regulation. It is concluded that PTEN selectively inhibits expression of VCAM-1 but not ICAM-1 through modulation of PI3K/Akt/GSK-3 beta/GATA-6 signaling cascade in TNF-alpha-treated ECs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：115 / 121

页数：7

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