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

Abstract : 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
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https://hal.inrae.fr/hal-03205339
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Submitted on : Thursday, April 22, 2021 - 11:26:57 AM
Last modification on : Tuesday, June 15, 2021 - 2:57:34 PM

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Guillaume Lezmi, Shamila Vibhushan, Claudia Bevilaqua, Nicolas Crapart, Nicolas Cagnard, et al.. Congenital cystic adenomatoid malformations of the lung: an epithelial transcriptomic approach. Respiratory Research, BioMed Central, 2020, 21 (1), ⟨10.1186/s12931-020-1306-5⟩. ⟨hal-03205339⟩

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