Hyperoxia impairs pro-angiogenic RNA production in preterm endothelial colony-forming cells

Megan A. Ahern, Claudine P. Black, Gregory J. Seedorf, Christopher D. Baker, Douglas P. Shepherd

Research output: Contribution to journalArticlepeer-review

Abstract

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 1a (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.

Original languageEnglish (US)
Pages (from-to)284-297
Number of pages14
JournalAIMS Biophysics
Volume4
Issue number2
DOIs
StatePublished - 2017

Keywords

  • Endothelial cell biology
  • Endothelial colony-forming cells
  • Fluorescence microscopy
  • Single-cell
  • Single-molecule

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

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