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.
Sequencing data has been uploaded to GEO (GSE145436), as mentioned in the manuscript 'Data and Materials Availability' section.
Short-term exposure to intermittent hypoxia in mice leads to changes in gene expression seen in chronic pulmonary diseaseNCBI Gene Expression Omnibus, GSE145436.
- David F Smith
- David F Smith
- David F Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Anurag Agrawal, CSIR Institute of Genomics and Integrative Biology, India
© 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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