Early-life ozone exposure modulates region-specific gene expression in the developing rat lung.

Autor: Stevens NC; Genome Center, University of California Davis, Davis, CA, USA., Edwards PC; Center for Health and the Environment, University of California Davis, Davis, CA, USA., Van Winkle LS; Center for Health and the Environment, University of California Davis, Davis, CA, USA; Department of Anatomy, Physiology and Cell Biology School of Veterinary Medicine, University of California Davis, Davis, CA, USA. Electronic address: lsvanwinkle@ucdavis.edu.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2023 Nov 01; Vol. 389, pp. 26-33. Date of Electronic Publication: 2023 Oct 21.
DOI: 10.1016/j.toxlet.2023.10.010
Abstrakt: Early-life ozone exposure disrupts normal patterns of lung development, but the molecular determinants underlying these changes are not well understood. This study aimed to elucidate changes in gene expression following episodic ozone exposure to identify potential mechanisms of ozone-mediated impairments in lung development. Rat pups were exposed to either filtered air or ozone (0.5 ppm, 6 hr./day, 5 days/week) from postnatal day (PND) 7-28 (16 dams total with 8 pups each, 4 M & 4 F) and sacrificed at either PND 30-31 or PND 80-84. Lung microdissection isolated major regions for RNA-Seq analysis. Ozone modified inherent differences in gene expression between lung regions in both male and female rat pups, whereas statistically significant changes in gene expression directly attributed to ozone were only identified in females. The greatest number of differentially expressed genes was observed between the distal airways and the parenchyma of ozone-exposed juvenile female rats, with 355 genes being differentially expressed. Genes modulating epithelial-to-mesenchymal transition, cell growth, and adhesion were differentially expressed in the parenchyma of ozone exposed juvenile females, suggesting that episodic ozone exposure may affect branching morphogenesis and lung cell growth. Importantly, our study provides novel targets for future experiments investigating the impact of ozone on lung development.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laura Van Winkle reports financial support was provided by National Institute of Environmental Health Sciences. Nathanial Stevens reports financial support was provided by National Heart Lung and Blood Institute. Nathanial Stevens reports financial support was provided by National Institute of Environmental Health Sciences. Laura Van Winkle reports financial support was provided by National Institutes of Health Office of the Director.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE