New insights on congenital pulmonary airways malformations revealed by proteomic analyses
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(2019) 14:272
RESEARCH
Open Access
New insights on congenital pulmonary airways malformations revealed by proteomic analyses C. Barazzone-Argiroffo1,2†, J. Lascano Maillard2†, I. Vidal3, M. L. Bochaton-Piallat2, S. Blaskovic2, Y. Donati2, B. E. Wildhaber3, A.-L. Rougemont4, C. Delacourt5,6 and I. Ruchonnet-Métrailler1,2*
Abstract Background: Congenital Pulmonary Airway Malformation (CPAM) has an estimated prevalence between 0.87 and 1.02/10,000 live births and little is know about their pathogenesis. To improve our knowledge on these rare malformations, we analyzed the cellular origin of the two most frequent CPAM, CPAM types 1 and 2, and compared these malformations with adjacent healthy lung and human fetal lungs. Methods: We prospectively enrolled 21 infants undergoing surgical resection for CPAM. Human fetal lung samples were collected after termination of pregnancy. Immunohistochemistry and proteomic analysis were performed on laser microdissected samples. Results: CPAM 1 and 2 express mostly bronchial markers, such as cytokeratin 17 (Krt17) or α-smooth muscle actin (ACTA 2). CPAM 1 also expresses alveolar type II epithelial cell markers (SPC). Proteomic analysis on microlaser dissected epithelium confirmed these results and showed distinct protein profiles, CPAM 1 being more heterogeneous and displaying some similarities with fetal bronchi. Conclusion: This study provides new insights in CPAM etiology, showing clear distinction between CPAM types 1 and 2, by immunohistochemistry and proteomics. This suggests that CPAM 1 and CPAM 2 might occur at different stages of lung branching. Finally, the comparison between fetal lung structures and CPAMs shows clearly different protein profiles, thereby arguing against a developmental arrest in a localized part of the lung. Keywords: Congenital pulmonary airways malformation, Lung malformations, Lung development, Proteomics
Introduction Lung development is a complex process allowing parenchymal architecture to evolve along the bronchial organization. To establish correct bud elongation and airway branching, cellular interactions between epithelial, endothelial and mesenchymal cells are required. These interactions are dependent on the paracrine secretion of different growth factors or transcription factors. Growth factors are classified into different groups based * Correspondence: [email protected] † These authors contributed equally to this work 1 Pediatric Pulmonology Unit, Department of Pediatrics,Obstetrics and Gynecology, Children’s Hospital, 6 Rue Willy Donzé, 1211 Geneva, Switzerland 2 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland Full list of author information is available at the end of the article
on their cell of origin, such as fibroblast growth factors (FGF), vascular growth factors (VEGF), and epithelial growth factors (EGF). Transcription factors, such as SOX2 and SOX9, are recognized to play a role in lung development and in particular during branching morphogenesis [1–5
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