Linked Life Data

20864106

Source:http://linkedlifedata.com/resource/pubmed/id/20864106

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pubmed-article:20864106pubmed:abstractTextPhosphotase 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-? in human endothelial cells (ECs). Transfection with PTEN overexpressing vector resulted in the significant decrease in phosphorylation of Akt in TNF-?-treated ECs. PTEN strongly inhibited VCAM-1 but not ICAM-1, however this inhibitory effect was reversed by co-transfection with constitutively active-Akt (CA-Akt-HA) in TNF-?-stimulated ECs. Additionally, silencing of PTEN with specific siRNA showed significant increase of phosphor-Akt compared with TNF-? alone treated ECs. siPTEN significantly upregulated VCAM-1 but was indifferent to ICAM-1 in TNF-?-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?) which is in turn regulated by PTEN-dependent Akt activity. Finally, PTEN significantly prevented monocyte adhesion to TNF-?-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?/GATA-6 signaling cascade in TNF-?-treated ECs.lld:pubmed
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pubmed-article:20864106pubmed:authorpubmed-author:ChangKi...lld:pubmed
pubmed-article:20864106pubmed:authorpubmed-author:SeoHan GeukHGlld:pubmed
pubmed-article:20864106pubmed:authorpubmed-author:KimHye JungHJlld:pubmed
pubmed-article:20864106pubmed:authorpubmed-author:KimYoung...lld:pubmed
pubmed-article:20864106pubmed:authorpubmed-author:LeeJae HeunJHlld:pubmed
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pubmed-article:20864106pubmed:authorpubmed-author:JangHwa JinHJlld:pubmed
pubmed-article:20864106pubmed:authorpubmed-author:ParkKyungokKlld:pubmed
pubmed-article:20864106pubmed:copyrightInfoCopyright © 2010 Elsevier Ireland Ltd. All rights reserved.lld:pubmed
pubmed-article:20864106pubmed:issnTypeElectroniclld:pubmed
pubmed-article:20864106pubmed:volume213lld:pubmed
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pubmed-article:20864106pubmed:pagination115-21lld:pubmed
pubmed-article:20864106pubmed:dateRevised2011-11-2lld:pubmed
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pubmed-article:20864106pubmed:year2010lld:pubmed
pubmed-article:20864106pubmed:articleTitlePTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3?/GATA-6 signaling pathways in TNF-?-activated human endothelial cells.lld:pubmed
pubmed-article:20864106pubmed:affiliationDepartment of Pharmacology, Institute of Health Sciences, School of Medicine, and Biomedical Center (BK21), Gyeongsang National University, 92 Chilam-dong, Jinju 660-751, Republic of Korea.lld:pubmed
pubmed-article:20864106pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20864106pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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