Endothelial to mesenchymal transition in neonatal hyperoxic lung injury: role of sex as a biological variable.
Physiol Genomics
; 55(8): 345-354, 2023 08 01.
Article
em En
| MEDLINE
| ID: mdl-37395632
ABSTRACT
Bronchopulmonary dysplasia (BPD) is characterized by an arrest in alveolarization, abnormal vascular development, and variable interstitial fibroproliferation in the premature lung. Endothelial to mesenchymal transition (EndoMT) may be a source of pathological fibrosis in many organ systems. Whether EndoMT contributes to the pathogenesis of BPD is not known. We tested the hypothesis that pulmonary endothelial cells will show increased expression of EndoMT markers upon exposure to hyperoxia and that sex as a biological variable will modulate differences in expression. Wild-type (WT) and Cdh5-PAC CreERT2 (endothelial reporter) neonatal male and female mice (C57BL6) were exposed to hyperoxia (0.95 [Formula see text]) either during the saccular stage of lung development (95% [Formula see text]; postnatal day 1-5 [PND1-5]) or through the saccular and early alveolar stages of lung development (75% [Formula see text]; PND1-14). Expression of EndoMT markers was measured in whole lung and endothelial cell mRNA. Sorted lung endothelial cells (from room air- and hyperoxia-exposed lungs) were subjected to bulk RNA-Seq. We show that exposure of the neonatal lung to hyperoxia leads to upregulation of key markers of EndoMT. Furthermore, using lung sc-RNA-Seq data from neonatal lung we were able to show that all endothelial cell subpopulations including the lung capillary endothelial cells show upregulation of EndoMT-related genes. Markers related to EndoMT are upregulated in the neonatal lung upon exposure to hyperoxia and show sex-specific differences. Mechanisms mediating EndoMT in the injured neonatal lung can modulate the response of the neonatal lung to hyperoxic injury and need further investigation.NEW & NOTEWORTHY We show that neonatal hyperoxia exposure increased EndoMT markers in the lung endothelial cells and this biological process exhibits sex-specific differences.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Displasia Broncopulmonar
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Hiperóxia
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Lesão Pulmonar
Limite:
Animals
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Female
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Humans
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Male
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Newborn
Idioma:
En
Revista:
Physiol Genomics
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos