New insights on congenital pulmonary airways malformations revealed by proteomic analyses

Abstract

BackgroundCongenital 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.MethodsWe 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.ResultsCPAM 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.ConclusionThis 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.

In vitro models of fetal lung development to enhance research into congenital lung diseases

“…This finding is an accordance with a previous report showing cystic malformation caused by deficiency of the Wnt receptor Frizzled 2 in branching airway epithelium [19]. With regard to transcription factors, diffuse expression of SOX9 and SOX2 in the epithelial cells lining the cystic lesion of CPAM type 1 and 2 have been reported [3,26]. This suggests disrupted regulation of the respective genes in the cystic lesions.…”

Application of second-generation sequencing in congenital pulmonary airway malformations

“…Finally, 860 up-regulated genes and 203 down-regulated genes were obtained. The sequence information of this whole transcript suggested that Nkx2-1 was normally expressed, Hoxb-5 was normally expressed and Sox2 was highly expressed, and the results were the same as those of other scholars 35 . BMPs belong to the TGF-β family, and several BMPs and their receptor BMPR play regulatory roles in lung development 1 , 35 .…”

Congenital malformation of the pulmonary airway (MCVAP), Case Report

“…El Tipo I es el más frecuente de las MCVAP y tiene el mejor pronóstico, debido a que son localizadas y solo afectan a una parte de un lóbulo, también puede ser multiloculados (4) . La mayoría está presente en el periodo neonatal o en el intrauterino, pero en casos infrecuentes puede presentarse más tarde.…”