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01-07-2015 | Original Article

Lower NPAS₃ expression during the later stages of abnormal lung development in rat congenital diaphragmatic hernia

Authors: Patrícia Pereira-Terra, Ramin Kholdebarin, Meghan Higgins, Barbara M. Iwasiow, Jorge Correia-Pinto, Richard Keijzer

Published in: Pediatric Surgery International | Issue 7/2015

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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Title: Lower NPAS3 expression during the later stages of abnormal lung development in rat congenital diaphragmatic hernia
Authors: Patrícia Pereira-Terra
Ramin Kholdebarin
Meghan Higgins
Barbara M. Iwasiow
Jorge Correia-Pinto
Richard Keijzer
Publication date: 01-07-2015
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 7/2015
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-015-3703-2

At a glance: The STEP trials

Springer Medicine

Lower NPAS₃ expression during the later stages of abnormal lung development in rat congenital diaphragmatic hernia

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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