Related Experiment Video For Congenital thoracic malformations
Updated: Dec 29, 2025
Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach
Guillaume Lezmi1,2,3, Shamila Vibhushan2, Claudia Bevilaqua4
1Service de Pneumologie et d'Allergologie Pédiatriques, AP-HP, Hôpital Universitaire Necker-Enfants Malades, 75743 Cedex 15, Paris, France.
Background:
The pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood.
Aim:
This study aimed to identify more precisely the molecular mechanisms limited to a compartment of lung tissue, through a transcriptomic analysis of the epithelium of macrocystic forms.
Methods:
Tissue fragments displaying CCAM were obtained during planned surgical resections. Epithelial mRNA was obtained from cystic and normal areas after laser capture microdissection (LCM). Transcriptomic analyses were performed and the results were confirmed by RT-PCR and immunohistochemistry in independent samples.
Results:
After controlling for RNA quality, we analysed the transcriptomes of six cystic areas and five control areas. In total, 393 transcripts were differentially expressed in the epithelium, between CCAM and control areas. The most highly redundant genes involved in biological functions and signalling pathways differentially expressed between CCAM and control epithelium included TGFB2, TGFBR1, and MAP 2 K1. These genes were considered particularly relevant as they have been implicated in branching morphogenesis. RT-qPCR analysis confirmed in independent samples that TGFBR1 was more strongly expressed in CCAM than in control tissues (p < 0.03). Immunohistochemistry analysis showed TGFBR1 (p = 0.0007) and TGFB2 (p < 0.02) levels to be significantly higher in the epithelium of CCAM than in that of control tissues.
Conclusions:
This compartmentalised transcriptomic analysis of the epithelium of macrocystic lung malformations identified a dysregulation of TGFB signalling at the mRNA and protein levels, suggesting a possible role of this pathway in CCAM pathogenesis.
Trial Registration:
ClinicalTrials.gov Identifier: NCT01732185.
