AI Article Synopsis
- Congenital diaphragmatic hernia (CDH) involves diaphragm defects, leading to underdeveloped lungs and high blood pressure in the lungs, with NPAS3 being a key factor in lung development.
- Researchers induced CDH in mice using nitrofen and analyzed NPAS3 expression in lung tissue at various stages of development.
- Results show that hypoplastic (underdeveloped) CDH lungs exhibited significantly reduced NPAS3 expression, indicating its potential role in the abnormal development associated with CDH.
Article Abstract
Purpose: Congenital diaphragmatic hernia (CDH) is characterized by a developmental defect in the diaphragm, pulmonary hypoplasia and pulmonary hypertension. NPAS3 is a PAS domain transcription factor regulating Drosophila tracheogenesis. NPAS3 null mice develop pulmonary hypoplasia in utero and die after birth due to respiratory failure. We aimed to evaluate NPAS3 expression during normal and abnormal lung development due to CDH.
Methods: CDH was induced by administering 100 mg/ml nitrofen to time-pregnant dams on embryonic day (E) 9 of gestation. Lungs were isolated on E15, E18 and E21 and NPAS3 localization was determined by immunohistochemistry and quantified using Western blotting.
Results: We found that only E21 hypoplastic CDH lungs have reduced expression of NPAS3 in the terminal saccules. Western blotting confirmed the down-regulation of NPAS3 protein in the nitrofen-induced hypoplastic lungs.
Conclusions: We demonstrate for the first time that nitrofen-induced hypoplastic CDH lungs have reduced NPAS3 expression in the terminal saccules during the later stages of abnormal lung development. Our findings suggest that NPAS3 is associated with pulmonary hypoplasia in CDH.
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| http://dx.doi.org/10.1007/s00383-015-3703-2 | DOI Listing |
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