Disruptions in the response of endothelial progenitor cells to changes in oxygen environment may present a possible mechanism behind multiple pediatric pulmonary disease models, such as bronchopulmonary dysplasia. Using high-throughput fixed single-cell protein and RNA imaging, we have created "stop-motion" movies of Thymosin. 4 (T beta 4) and Hypoxia Inducible Factor 1 alpha (HIF-1 alpha) protein expression and vascular endothelial growth factor (vegf) and endothelial nitric oxide synthase (eNOS) mRNA in human umbilical cord-derived endothelial colony-forming cells (ECFC). ECFC were grown in vitro under both room air and hyperoxia (50% O-2). We find elevated basal T beta 4 protein expression in ECFC derived from prematurely born infants versus full term infants. T beta 4 is a potent growth hormone that additionally acts as an actin sequestration protein and regulates the stability of HIF-1 alpha. This basal level increase of T beta 4 is associated with lower HIF1 alpha nuclear localization in preterm versus term ECFC upon exposure to hyperoxia. We find altered expression in the pro-angiogenic genes vegf and eNOS, two genes that HIF-1 alpha acts as a transcription factor for. This provides a potential link between a developmentally regulated protein and previously observed impaired function of preterm ECFC in response to hyperoxia.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/626103 |
| Date | January 2017 |
| Creators | A. Ahern, Megan, P. Black, Claudine, J. Seedorf, Gregory, D. Baker, Christopher, P. Shepherd, Douglas |
| Contributors | Univ Arizona, Dept Physiol |
| Publisher | AMER INST MATHEMATICAL SCIENCES-AIMS |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2017 Douglas P. Shepherd, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License. |
| Relation | http://www.aimspress.com/article/10.3934/biophy.2017.2.284 |
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