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01-11-2013 | Original Article

Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs

Authors: Hiromizu Takahashi, Florian Friedmacher, Naho Fujiwara, Alejandro Hofmann, Balazs Kutasy, Jan-Hendrik Gosemann, Prem Puri

Published in: Pediatric Surgery International | Issue 11/2013

Abstract

Purpose

Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs.

Methods

Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(−)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution.

Results

Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(−) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls.

Conclusion

Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular–saccular stages may interfere with saccular–alveolar differentiation and distal airway maturation resulting in PH.

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Title: Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs
Authors: Hiromizu Takahashi
Florian Friedmacher
Naho Fujiwara
Alejandro Hofmann
Balazs Kutasy
Jan-Hendrik Gosemann
Prem Puri
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 11/2013
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-013-3387-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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