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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0044602,
umls-concept:C0063695,
umls-concept:C0078056,
umls-concept:C0086418,
umls-concept:C0086982,
umls-concept:C0185117,
umls-concept:C0225336,
umls-concept:C0244989,
umls-concept:C0285761,
umls-concept:C0694888,
umls-concept:C0851285,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1705325,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
1
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pubmed:dateCreated |
2010-10-25
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pubmed:abstractText |
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-? 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GATA6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1879-1484
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
213
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
115-21
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:20864106-Cells, Cultured,
pubmed-meshheading:20864106-GATA6 Transcription Factor,
pubmed-meshheading:20864106-Gene Expression Regulation,
pubmed-meshheading:20864106-Glycogen Synthase Kinase 3,
pubmed-meshheading:20864106-Humans,
pubmed-meshheading:20864106-Intercellular Adhesion Molecule-1,
pubmed-meshheading:20864106-PTEN Phosphohydrolase,
pubmed-meshheading:20864106-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20864106-Phosphorylation,
pubmed-meshheading:20864106-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20864106-RNA, Small Interfering,
pubmed-meshheading:20864106-Signal Transduction,
pubmed-meshheading:20864106-Tumor Necrosis Factor-alpha,
pubmed-meshheading:20864106-Vascular Cell Adhesion Molecule-1
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pubmed:year |
2010
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pubmed:articleTitle |
PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3?/GATA-6 signaling pathways in TNF-?-activated human endothelial cells.
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pubmed:affiliation |
Department 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.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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