Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease
- Cincinnati Children's Hospital Medical Center, United States
- University of Cincinnati College of Medicine, United States
Abstract
Obstructive sleep apnea (OSA) results from episodes of airway collapse and intermittent hypoxia (IH) and is associated with a host of health complications. Although the lung is the first organ to sense changes in oxygen levels, little is known about the consequences of IH to the lung hypoxia-inducible factor- (HIF)-responsive pathways. We hypothesized that exposure to IH would lead to cell-specific up and downregulation of diverse expression pathways. We identified changes in circadian and immune pathways in lungs from mice exposed to IH. Among all cell types, endothelial cells showed the most prominent transcriptional changes. Upregulated genes in myofibroblast cells were enriched for genes associated with pulmonary hypertension and included targets of several drugs currently used to treat chronic pulmonary diseases. A better understanding of the pathophysiologic mechanisms underlying diseases associated with OSA could improve our therapeutic approaches, directing therapies to the most relevant cells and molecular pathways.
Data availability
Sequencing data has been uploaded to GEO (GSE145436), as mentioned in the manuscript 'Data and Materials Availability' section.
Article and author information
Author details
Funding
National Institutes of Health (5K08HL148551-02)
- David F Smith
American Laryngological, Rhinological and Otological Society (2017 Career Development Award)
- David F Smith
American Society of Pediatric Otolaryngology (2016 Basic Research Award)
- David F Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anurag Agrawal, CSIR Institute of Genomics and Integrative Biology, India
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#2019-0028) of the Cincinnati Children's Hospital Medical Center.
Version history
- Received: September 11, 2020
- Accepted: February 17, 2021
- Accepted Manuscript published: February 18, 2021 (version 1)
- Accepted Manuscript updated: February 19, 2021 (version 2)
- Version of Record published: February 26, 2021 (version 3)
Copyright
© 2021, Wu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease
eLife 10:e63003.
https://doi.org/10.7554/eLife.63003
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