The essential role of cytoskeleton and ciliary system alterations in the development of congenital pulmonary airway malformations

Purpose Congenital pulmonary airway malformation (CPAM) is a developmental lung malformation that seriously endangers children's health. The objective of this study was to investigate the etiology of CPAM by observing changes at the molecular and cellular levels.Methods Patient clinical data were collected and analyzed. Tissue samples were collected from CPAM lesions and marginal normal lung tissue during CPAM surgery. The samples were subjected to H&E staining for pathological analysis. Tissue RNA was isolated for RNA sequencing, and the differentially expressed genes (DEGs) were enriched for Gene Ontology (GO) analysis. The cytoskeletal and cell subtypes were subjected to immunofluorescence staining.ResultsRNA sequencing of 7 CPAM patients revealed 1252 DEGs, with 1041 upregulated and 211 downregulated. GO analysis revealed that biological processes related to cilium organization and movement were strongly enriched. Protein‒protein interaction (PPI) network analysis highlighted genes such as BMP2, TNF, DNAI1, DNAI2, and DNAH5 as potentially important in CPAM. Immunofluorescence staining revealed abnormalities in the cytoskeleton and a reduction in the number of alveolar epithelial type II (AEC II) cells in CPAM lesions compared with normal lung tissue.Conclusion Our study revealed that CPAM is associated with a significant increase in cytoskeletal elements and a decrease in AEC IIs, along with an abnormal increase in the expression of cilium-related genes. These alterations provide critical insights into the etiology of CPAM and may guide the development of improved diagnostic and therapeutic strategies for this condition.