A prenatally disrupted airway epithelium orchestrates the fetal origin of asthma in mice
Beteiligte Einrichtungen
Abstract
OBJECTIVE: Here we have aimed to identify the differential sex-specific effects of prenatal challenges on lung function, immune response, and asthma severity in mice.
METHODS: We generated bone marrow chimeric (BMC) mice harboring either prenatally stress-exposed lungs or a prenatally stress-exposed immune (hematopoietic) system and induced allergic asthma via ovalbumin. Next-generation sequencing (RNA sequencing) of lungs and assessment of airway epithelial barrier function in ovalbumin-sensitized control and prenatally stressed offspring was also performed.
RESULTS: Profoundly enhanced airway hyperresponsiveness, inflammation, and fibrosis were exclusively present in female BMC mice with prenatally stress-exposed lungs. These effects were significantly perpetuated if both the lungs and the immune system had been exposed to prenatal stress. A prenatally stress-exposed immune system alone did not suffice to increase the severity of these asthma features. RNA sequencing analysis of lungs from prenatally stressed, non-BMC, ovalbumin-sensitized females unveiled a deregulated expression of genes involved in asthma pathogenesis, tissue remodeling, and tight junction formation. It was also possible to independently confirm a tight junction disruption. In line with this, we identified an altered perinatal and/or postnatal expression of genes involved in lung development along with an impaired alveolarization in female prenatally stressed mice.
CONCLUSION: Here we have shown that the fetal origin of asthma is orchestrated by a disrupted airway epithelium and further perpetuated by a predisposed immune system.
Bibliografische Daten
Originalsprache | Englisch |
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ISSN | 0091-6749 |
DOIs | |
Status | Veröffentlicht - 06.2020 |
Anmerkungen des Dekanats
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PubMed | 32305348 |
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