Atypical mesenchyme in congenital pulmonary airways malformation: a promising new focus

Article Article scientifique Article Atypical mesenchyme in congenital pulmonary airways malformation: a promising new focus eng 2025-08-26 author Azar Pascal 0000-0002-0022-0367 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 970290 Département de pathologie et immunologie (PATIM) author Ventura Avila Yannick Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 683616 author Hiltbrunner Anita Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 28570 Département de pathologie et immunologie (PATIM) author Delacourt Christophe Pediatric Pulmonology Unit, Center for Rare Respiratory Diseases in Children (RESPIRARE), APHP, Necker-Enfants Malades Hospital, Paris-Cité University, Paris, France. author Rougemont-Pidoux Anne-Laure Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Division of Clinical Pathology, Diagnostic Department, Pediatric and Fetoplacental Pathology Unit, University Hospital of Geneva, Geneva, Switzerland. 29140 Département de pathologie et immunologie (PATIM) author Andrieu Vidal Isabelle Department of Pediatrics, Gynecology and Obstetrics, Division of Child and Adolescent Surgery, University Hospital of Geneva, Geneva, Switzerland. 749564 author Piallat Marie-Luce 0000-0001-8408-8932 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 23951 Département de pathologie et immunologie (PATIM) author Ruchonnet Isabelle 0000-0003-4771-875X Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. isabelle.ruchonnet-metrailler@hug.ch.,Department of Pediatrics, Gynecology, and Obstetrics, Pediatric Pulmonolgy Unit, University Hospital of Geneva, Geneva, Switzerland. isabelle.ruchonnet-metrailler@hug.ch. 106509 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) 262 10.1186/s12931-025-03332-4 40859353 1465-9921 PMC12382140 https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-025-03332-4 Background: Congenital pulmonary airways malformations (CPAM) belong to a group of rare congenital lung anomalies whose pathological origin is still mostly unknown. The current research project aims to study the possible role of the underlying mesenchyme in CPAM pathophysiology by comparing data from fetal tissue and healthy lung with CPAM. Methods: Tissue samples from CPAM patients and healthy adjacent parts were collected during planned surgical resections. Fetal lung tissue obtained from abortions was also used. The mesenchymal parts of pathological, healthy and fetal lung tissues were analyzed using quantitative proteomic, bulk RNA sequencing and multiplex immunohistochemistry to identify the difference in genes and proteins expressed in CPAM. Results: When compared to healthy adjacent lung tissue, transcriptomic data of CPAM tissue highlighted downregulation of genes implicated in the transforming-growth factor-β and immune-related signaling pathways. Conversely, epithelial-mesenchymal transition genes were upregulated in CPAM, suggesting an abnormal branching associated with abnormal mesenchyme. Quantitative proteomic results showed that the expression of various proteins implicated in muscle differentiation, such as desmin, calponin1 and α-smooth muscle actin, were decreased in CPAM compared to healthy adjacent lung. Multiplex immunostaining confirmed these results with a more significant difference for CPAM type 1 compared to healthy adjacent tissue or to fetal lung. Several pathways known to be crucial in epithelial proliferation, differentiation or branching such as PI3K-AKT-mTOR pathway were dampened. Conclusion: Our study reveals the presence of abnormal mesenchyme and muscle in and surrounding cystic tissue. Despite normal lung function during pediatric follow-up, the atypical mesenchyme with possible impaired epithelial-mesenchymal transition could potentially contribute to the development of late adult pathologies such as chronic obstructive pulmonary disease or lung tumors and should be assessed accordingly. CPAM Human Mesenchyme Proteomic Transcriptomic Translational Dewey 616.07 Dewey 618 137 Département de pathologie et immunologie 21F 58 Département de pédiatrie, gynécologie et obstétrique 223 false 380 Bochaton-Piallat Marie-Luce (pathologie et immunologie) 646 Respiratory research 26 1 5559626d-4b1f-49f3-b434-e271f08e1ca4 Article (Published version) Public Article_scientifique_from_crossref.pdf 2388891 application/pdf CC BY-NC-ND-4.0 ffd6469eb24078253c2d9222e03dc65498fb6f370381d6b9443748236049be48 74eaa4d2-de41-4618-ab8a-41225da12eb1 Supplemental data Public 12931_2025_3332_MOESM1_ESM.jpg 129698 image/jpeg a54f385863a40b2832d303a7bb85c8674022daa7da4eb6cef8bcefcd7818f4d5 2d7624a1-74f2-4621-a9ca-7ca5aa721e62 Supplemental data Public 12931_2025_3332_MOESM2_ESM.docx 14626 application/vnd.openxmlformats-officedocument.wordprocessingml.document 5afac8573ee45295c287f761fda49f9300efa991a494489185f73293a2172bd4 bba5f97f-81f1-4a3d-848b-9a6be499ab78 Supplemental data Public 12931_2025_3332_MOESM3_ESM.docx 14656 application/vnd.openxmlformats-officedocument.wordprocessingml.document c16f6e0f96c0e13a98024811c483a9232f55c299f7633c591194d4a468d6c3c2 82f9ad85-6ede-4285-a330-e11323876f64 Supplemental data Public 12931_2025_3332_MOESM4_ESM1.xlsx 1628528 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet ef7c41b092eb339e89743a0cdafe2084a93ef5933b4b9809d303fcf2e7fe6f7f fde5b70f-4a22-4b2e-a681-8400745f6b35 Supplemental data Public 12931_2025_3332_MOESM5_ESM.xlsx 169475 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 759dbe0411acfb7f83c42869a30f6adc214c79c203c39423296326b90c65e2e4 ad2c2f58-1910-4eeb-844c-0302e18daf73 Supplemental data Public 12931_2025_3332_MOESM6_ESM.xlsx 32934 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet d904f1330e8864140dba3bf942853570c66b90300cba20d9b98823c86c6e5559 585a4c8b-4c89-483c-a072-d9d8905a1aed Supplemental data Public 12931_2025_3332_MOESM7_ESM.jpg 62537 image/jpeg c1f949ada12e877c54a8137bf090bb6fcb7f2fc072a4df79377d1f049658322a 514b53ed-aec4-4569-89f3-f13c04208b58 Supplemental data Public 12931_2025_3332_MOESM8_ESM.jpg 36031 image/jpeg 134c49f53e1c184c9b5af2625266728c64d66e354b46072167f43943ab98d272 openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

Title	Published in	Year	Views	Downloads

Atypical mesenchyme in congenital pulmonary airways malformation: a promising new focus	Respiratory research	2025	41	195
Smooth muscle actin isoforms: a tug of war between contraction and compliance	European journal of cell biology	2013	673	0

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