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The proportion of alveolar type 1 cells decreases in murine hypoplastic congenital diaphragmatic hernia lungs.
- Source :
-
PloS one [PLoS One] 2019 Apr 17; Vol. 14 (4), pp. e0214793. Date of Electronic Publication: 2019 Apr 17 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Background: Pulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs.<br />Objective: We used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors.<br />Study Design: Pregnant Swiss mice were gavage-fed with nitrofen/bisdiamine or vehicle at embryonic day 8.5. The administered dose was optimized by assessing the survival, congenital diaphragmatic hernia and facial abnormality rates of the exposed mouse pups. NanoCT was performed on embryonic day 11.5 and 16.5 to assess the embryonic and early canalicular stages of lung development. At embryonic day 17.5 corresponding to late canalicular stage, congenital diaphragmatic hernia lungs were characterized by measuring the lung weight/body weight ratio, morphometry, epithelial cell marker gene expression levels and alveolar cell type quantification.<br />Results: Nitrofen/bisdiamine associated congenital diaphragmatic hernia lungs showed delayed development, hypoplasia with morphologic immaturity and thickened alveolar walls. Expression levels of distal epithelial progenitor marker Id2 increased, alveolar type 1 cell markers Pdpn and Hopx decreased, while type 2 cell markers pro-SPC and Muc1 remained constant during the canalicular stage. The number of Pdpn+ type 1 alveolar cells also decreased in congenital diaphragmatic hernia lungs.<br />Conclusion: The mouse nitrofen/bisdiamine model is a potential model allowing the study of congenital diaphragmatic hernia lung development from early stages using a wide array of methods. Based on this model, the alveolar epithelium showed a decrease in the number of alveolar type 1 cell in congenital diaphragmatic hernia lungs while type 2 cell population remains unchanged.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Alveolar Epithelial Cells metabolism
Animals
Cell Count
Cell Differentiation
Diamines toxicity
Disease Models, Animal
Embryonic Stem Cells metabolism
Embryonic Stem Cells pathology
Female
Hernias, Diaphragmatic, Congenital chemically induced
Hernias, Diaphragmatic, Congenital embryology
Lung embryology
Lung pathology
Mice
Organ Size
Phenyl Ethers toxicity
Pregnancy
Teratogens toxicity
Alveolar Epithelial Cells pathology
Hernias, Diaphragmatic, Congenital pathology
Lung abnormalities
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 30995255
- Full Text :
- https://doi.org/10.1371/journal.pone.0214793