Open AccessHyperoxia impairs pro-angiogenic RNA production in preterm endothelial colony-forming cells
Author(s) -
Megan A. Ahern,
Claudine P. Black,
Gregory J. Seedorf,
Christopher D. Baker,
Douglas P. Shepherd
Publication year - 2017
Publication title -
aims biophysics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.545
H-Index - 12
ISSN - 2377-9098
DOI - 10.3934/biophy.2017.2.284
Subject(s) - hyperoxia , enos , biology , vascular endothelial growth factor , microbiology and biotechnology , bronchopulmonary dysplasia , progenitor cell , endothelial stem cell , nitric oxide , cancer research , nitric oxide synthase , medicine , stem cell , endocrinology , in vitro , lung , biochemistry , genetics , vegf receptors , pregnancy , gestational age
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 β4 (Tβ4) and Hypoxia Inducible Factor 1α (HIF-1α) 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% O2). We find elevated basal Tβ4 protein expression in ECFC derived from prematurely born infants versus full term infants. Tβ4 is a potent growth hormone that additionally acts as an actin sequestration protein and regulates the stability of HIF-1α. This basal level increase of Tβ4 is associated with lower HIF-1α 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-1α 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