The effects of tracheal occlusion on Wnt signaling in a rabbit model of congenital diaphragmatic hernia

Abstract

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.

Surgical technique for developing a rabbit model of congenital diaphragmatic hernia and tracheal occlusion

“…This surgical technique of CDH creation resulted in lung hypoplasia which was reversed by tracheal occlusion [16]. This was recently validated in our research on the effects of tracheal occlusion on Wnt signaling in a rabbit model of CDH [16].…”

Lnc90386 Sponges miR-33-5p to Mediate Mycoplasma gallisepticum-Induced Inflammation and Apoptosis in Chickens via the JNK Pathway

“…miR-33 has been reported to regulate inflammatory responses, cellular function and gene expression ( 41 , 42 ). Importantly, dysregulation of miR-33 has been frequently reported to be closely associated with respiratory disease and pathogenic microbial infections ( 43 , 44 ). For example, miR-33 suppresses LPS-stimulated production of pro-inflammatory factor (TNF-α and IL-1β) in macrophages by inhibiting RIP140 expression ( 45 ).…”

Fetal lung regeneration using stem cell‐derived extracellular vesicles: A new frontier for pulmonary hypoplasia secondary to congenital diaphragmatic hernia

“…29 Alongside studies analyzing samples from human CDH patients, there has been extensive literature on experimental models confirming that highly conserved miRNAs play a role in the pathogenesis of CDH associated lung underdevelopment. [29][30][31][32][33][34][35][36][37][38] One could envision that a therapy that supplements the missing miRNAs could be a potential therapeutic strategy to rescue lung underdevelopment in CDH babies (Figure 1). Given the myriad of known and unknown miRNA candidates and the complex pathological phenotype observed in CDH hypoplastic lungs, a promising avenue could be a therapy based on the administration of extracellular vesicles (EVs) that deliver a heterogenous complement of small RNA species.…”