PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3 beta/GATA-6 signaling pathways in TNF-alpha-activated human endothelial cells
- Authors
- Tsoyi, Konstantin; Jang, Hwa Jin; Nizamutdinova, Irina Tsoy; Park, Kyungok; Kim, Young Min; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Chang, Ki Churl
- Issue Date
- Nov-2010
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Adhesion molecules; Tumor necrosis factor-alpha; PTEN; Endothelial cells; GATA; Atherosclerosis
- Citation
- ATHEROSCLEROSIS, v.213, no.1, pp.115 - 121
- Indexed
- SCIE
SCOPUS
- Journal Title
- ATHEROSCLEROSIS
- Volume
- 213
- Number
- 1
- Start Page
- 115
- End Page
- 121
- URI
- https://scholarworks.bwise.kr/gnu/handle/sw.gnu/24879
- DOI
- 10.1016/j.atherosclerosis.2010.07.061
- ISSN
- 0021-9150
- Abstract
- 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.
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