The Effects of Tracheal Occlusion on Wnt Signaling in a Rabbit Model of Congenital Diaphragmatic Hernia

Purpose: Tracheal occlusion (TO) reverses pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH), but its effect on epithelial-mesenchymal transition (EMT) in lung development remains poorly understood. The purpose of this study was to a) confirm the CDH rabbit model produced PH which was reversed by TO and b) determine the effects of CDH +/- TO on EMT pathways. Methods: CDH was created at 23 days, TO at 28 days and lung collection at 31 days gestation in fetal rabbits. Lung body weight ratio (LBWR), mean terminal bronchiole density (MTBD), and expression of mRNA and micro-RNA was determined. Results: Fifteen CDH, 15 CDH+TO, 6 sham CDH, and 15 controls were included in the study. LBWR was low in CDH while CDH+TO was similar to controls. MTBD was higher in CDH fetuses and restored to control levels in CDH+TO. miR-33 and MKI67 were increased following TO, while Lgl1 was decreased in CDH+TO. Conclusion: TO reversed PH and stimulated early Wnt signaling in CDH fetal rabbits.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Surgery

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2018

Author dc:creator

• Mudri, Martina M

Advisors dc:contributor.advisor

• Bütter, Andreana
• Regnault, Timothy R.H.

• Congenital diaphragmatic hernia (CDH)
• tracheal occlusion (TO)
• epithelial-mesenchymal transition (EMT)
• lung development
• Wnt signaling
• micro-RNA

Language dc:language.iso

en_ca

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/28345

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/28345