Abstract
Previous studies have shown that endothelial colony forming cells (ECFCs) play an important role in the neovascularization of tumors. Hypoxia is emphasized as an important promoter of angiogenesis. However, little is known about genome-wide transcriptional regulation of ECFCs under hypoxic conditions. In this study, gene expression profiles in ECFCs were evaluated under hypoxic conditions for 3, 6, 12, 24, and 48 h, using Affymetrix U133 plus 2.0 chip microarray. 1,103 hypoxia-regulated genes were filtered, with 379 (0.693 %) genes up-regulated and 724 (1.32 %) genes down-regulated. Most of the up-regulated genes were involved in apoptosis, cell proliferation, or metabolic processes, while most of the down-regulated genes were involved in cell adherence, cell cycle, DNA and mRNA metabolic processes, multi-cellular organism development, protein metabolic processes, response to stress, signal transduction, or transport. This expression profile is ECFC-specific, because it is significantly different from those of endothelial cells and smooth muscle cells under hypoxic conditions. Moreover, hypoxia-regulated apoptosis in ECFCs is mainly related with the mitochondrial pathway (p53-BAX-Caspase-9) and the death receptor pathway (FAS-Caspase-8-Caspase-3). MAPK pathway is activated in ECFCs under hypoxic conditions. The differentially expressed genes of ECFCs were identified under hypoxic conditions, and related with cell apoptosis, cell cycle and MAPK pathways, shedding light on the mechanism of angiogenesis.
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Acknowledgments
This study was supported by the Grants for Natural Science grants in Jiangsu Province (BK200862), Outstanding Physicians in Jiangsu Province, National Natural Science Foundation of China (General Program; 30972904, 81201621). And thank GENG Tuo-yu in Medical University of South Carolina (MUSC) for the discussion about this study, and Thomas G. Smith of the MUSC Writing Centers for editing the manuscript.
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De-Cai Yu and Wen-Du Feng contributed equally to this study.
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13258_2012_55_MOESM2_ESM.xls
Supplementary material Supplementary Table 1. The information of 1,103 hypoxia-inducible differentially expressed genes (XLS 472 kb)
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Yu, DC., Feng, WD., Shi, XB. et al. Dynamic analysis for gene expression profiles of endothelial colony forming cells under hypoxia. Genes Genom 35, 451–462 (2013). https://doi.org/10.1007/s13258-012-0055-3
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DOI: https://doi.org/10.1007/s13258-012-0055-3