Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach

Autor: Naziha Khen-Dunlop, Christophe Delacourt, Shamila Vibhushan, Guillaume Lezmi, Nicolas Crapart, Claudia Bevilaqua, Alice Hadchouel, Nicolas Cagnard, Christine Boyle-Freyssaut
Přispěvatelé: Service de Pneumologie et d'Allergologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5), Génétique Animale et Biologie Intégrative (GABI), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie pédiatrique [CHU Necker], APHP-Programme Hospitalier de Recherche Clinique (PHRC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Lallemant, Christopher, AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Pathology
medicine.medical_specialty
[SDV]Life Sciences [q-bio]
Kruppel-Like Transcription Factors
Laser Capture Microdissection
Respiratory Mucosa
Biology
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Transcriptome
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Cystic Adenomatoid Malformation of Lung
Congenital
medicine
Humans
Prospective Studies
RNA
Messenger
Gene
Laser capture microdissection
lcsh:RC705-779
Messenger RNA
Lung
Research
Gene Expression Profiling
Infant
Cystic lung
lcsh:Diseases of the respiratory system
Epithelium
030104 developmental biology
medicine.anatomical_structure
Early Growth Response Transcription Factors
Congenital thoracic malformations
[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Immunohistochemistry
Female
Transforming growth factor
030217 neurology & neurosurgery
Follow-Up Studies
Zdroj: Respiratory Research
Respiratory Research, BioMed Central, 2020, 21 (1), ⟨10.1186/s12931-020-1306-5⟩
Respiratory Research, BioMed Central, 2020, 21 (1), pp.43. ⟨10.1186/s12931-020-1306-5⟩
Respiratory Research, Vol 21, Iss 1, Pp 1-10 (2020)
ISSN: 1465-993X
1465-9921
DOI: 10.1186/s12931-020-1306-5⟩
Popis: BackgroundThe pathophysiology of congenital cystic adenomatoid malformations (CCAM) of the lung remains poorly understood.AimThis 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.MethodsTissue 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.ResultsAfter 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 includedTGFB2, TGFBR1, andMAP 2 K1. These genes were considered particularly relevant as they have been implicated in branching morphogenesis. RT-qPCR analysis confirmed in independent samples thatTGFBR1was more strongly expressed in CCAM than in control tissues (p p = 0.0007) and TGFB2 (p ConclusionsThis 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 registrationClinicalTrials.gov Identifier:NCT01732185.
Databáze: OpenAIRE
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