Eur J Pediatr Surg 2014; 24(01): 075-078
DOI: 10.1055/s-0033-1351392
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Pulmonary FGF9 Gene Expression is Downregulated during the Pseudoglandular Stage in Nitrofen-Induced Hypoplastic Lungs

Hiromizu Takahashi
1  National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
2  Department of General Medicine, Juntendo University School of Medicine, Tokyo, Japan
,
Florian Friedmacher
1  National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
,
Naho Fujiwara
1  National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
,
Alejandro Hofmann
1  National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
,
Prem Puri
1  National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland
3  Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
› Author Affiliations
Further Information

Publication History

15 May 2013

26 June 2013

Publication Date:
29 July 2013 (online)

Abstract

Introduction The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) remains unclear. Fibroblast growth factor 9 (FGF9) is an essential component of the gene network that regulates lung development. FGF9 knockouts exhibit disrupted mesenchymal proliferation and reduced airway branching. The authors hypothesized that pulmonary FGF9 gene expression is downregulated during the pseudoglandular stage in nitrofen-induced hypoplastic lungs.

Material and Methods Pregnant rats received either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were dissected on D15 and D18, and were divided into controls, hypoplastic lungs with CDH (CDH+) and hypoplastic lungs without CDH (CDH−). Pulmonary FGF9 gene expression levels were analyzed by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed to investigate FGF9 protein expression/distribution.

Results Relative messenger RNA levels of FGF9 were significantly decreased on D15 in hypoplastic lungs compared with controls (p < 0.01), and on D18 in CDH+ and CDH− compared with controls (p < 0.05, respectively). Immunoreactivity of FGF9 was markedly diminished in mesothelium and distal airway epithelium on D15 and decreased in overall intensity on D18 in hypoplastic lungs compared with controls.

Conclusions Downregulation of FGF9 gene expression during the pseudoglandular stage may cause pulmonary hypoplasia in the nitrofen model by decreasing distal airway epithelial and mesenchymal proliferation throughout the branching morphogenesis.