Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach.
Cystic Adenomatoid Malformation of Lung, Congenital
/ genetics
Early Growth Response Transcription Factors
/ biosynthesis
Female
Follow-Up Studies
Gene Expression Profiling
/ methods
Humans
Infant
Kruppel-Like Transcription Factors
/ biosynthesis
Laser Capture Microdissection
/ methods
Male
Prospective Studies
RNA, Messenger
/ biosynthesis
Respiratory Mucosa
/ metabolism
Congenital thoracic malformations
Cystic lung
Laser capture microdissection
Transcriptome
Transforming growth factor
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
04 Feb 2020
04 Feb 2020
Historique:
received:
05
11
2019
accepted:
27
01
2020
entrez:
6
2
2020
pubmed:
6
2
2020
medline:
24
11
2020
Statut:
epublish
Résumé
The pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood. 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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT01732185.
Sections du résumé
BACKGROUND
BACKGROUND
The pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood.
AIM
OBJECTIVE
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
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
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
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
BACKGROUND
ClinicalTrials.gov Identifier: NCT01732185.
Identifiants
pubmed: 32019538
doi: 10.1186/s12931-020-1306-5
pii: 10.1186/s12931-020-1306-5
pmc: PMC7001206
doi:
Substances chimiques
Early Growth Response Transcription Factors
0
KLF10 protein, human
0
Kruppel-Like Transcription Factors
0
RNA, Messenger
0
Banques de données
ClinicalTrials.gov
['NCT01732185']
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
43Subventions
Organisme : Assistance Publique - Hôpitaux de Paris
ID : PHRC 2012-A00538-35
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