Transcriptome of angiopoietin 1-activated human umbilical vein endothelial cells.
Angiopoietin 1 (Ang-1) is the main ligand for endothelial cell-specific tyrosine kinase (Tie-2) receptors and it promotes migration and proliferation and inhibits apoptosis and vascular leakage. The exact mechanisms through which the Ang-1 exerts these effects remain unclear. The authors exposed human umbilical vein endothelial cells (HUVECs) to Ang-1 (300 ng/mL) for 4 h and conducted gene expression profiling using oligonucleotide microarrays. Real-time polymerase chain reaction (PCR) was also conducted to verify several of the genes that were regulated by Ang-1. Exposure to Ang-1 resulted in induction of 86 genes that are involved in endothelial cell (EC) proliferation, differentiation, migration, and survival. Thirty-six of these genes, including stanniocalcin, cyclin D1, vascular endothelial growth factor C, fms-related tyrosine kinase 1, interleukin 8, and CXCR4 have previously been shown to be induced by vascular endothelial growth factor (VEGF), suggesting significant similarities between VEGF and Ang-1 pathways. Ang-1 exposure also inhibited mRNA expressions of 49 genes, most of which are involved in cell cycle arrest, apoptosis, and suppression of transcription. These results indicate that Ang-1 triggers coordinated responses in endothelial cells designed to inhibit the expression of proapoptotic and antiproliferative genes and up-regulate proproliferative, proangiogenic, and antiapoptotic pathways. Moreover, we also found that the Erk1/2, phosphatidylinositol (PI) 3-kinase, and the mTOR pathways are involved in Ang-1-induced gene expression in HUVECs.
Abdel-Malak
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NA
Critical Care and Respiratory Divisions, Royal Victoria Hospital, and Meakins-Christie Laboratories, McGill University Health Centre, McGill University, Montreal, Québec, Canada.
Harfouche
R
R
Hussain
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D000730:Androstadienes / Q000494:pharmacology; D042683:Angiopoietin-1 / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014471:Umbilical Veins / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D042683:Angiopoietin-1; D005419:Flavonoids; D016209:Interleukin-8; D012333:RNA, Messenger; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus; D000077191:Wortmannin