Epithelial cell-adhesion protein cadherin 26 is dysregulated in congenital diaphragmatic hernia and congenital pulmonary airway malformation.

BACKGROUND: Congenital diaphragmatic hernia (CDH) and congenital pulmonary airway malformation (CPAM) are two inborn pathologies of the lung of unknown origin. Alterations of gene expression in airway epithelial cells are involved in the pathobiology of both diseases. We previously found decreased expression of the epithelial cell adhesion protein cadherin 26 (CDH26) in hypoplastic mice lungs. Here, our objective was to describe the expression and localization of CDH26 in hypoplastic CDH lungs and hyperproliferative CPAM tissues. METHODS: After ethical approval, we used human lung tissues from CDH and CPAM cases and age-matched control samples from a previously established biobank. Furthermore, lungs from the nitrofen rat model of CDH were included in the study. We performed immunohistochemistry and western blot analysis with antibodies against CDH26 to examine protein localization and abundance. Statistical analysis was performed using Mann-Whitney U test with significance set at p < 0.05. RESULTS: We observed an overexpression of CDH26 within the epithelium of cystic CPAM lesions compared to normal airways within the same lung and compared to control lungs. Western blot demonstrated a downregulation of CDH26 in the nitrofen rat model of CDH compared to healthy controls. Immunohistochemistry could not show consistent differences between CDH and control in human and rat lungs. In the studied human lung samples, CDH26 was localized to the apical part of the airway epithelial cells. CONCLUSION: CDH26 is differentially expressed in human CPAM lung tissues and may be downregulated in nitrofen-induced hypoplastic rat lungs compared to control lungs. Disruption of CDH26 associated pathways in lung development may be involved in the pathogenesis of lung hypoplasia or cystic lung disease.

Establishment of a biobank for human lung tissues of congenital diaphragmatic hernia and congenital pulmonary airway malformation.

BACKGROUND: Human tissue samples are an invaluable and little available source of information for translational studies of congenital lung diseases such as Congenital Diaphragmatic Hernia (CDH) or Congenital Pulmonary Airway Malformation (CPAM). PURPOSE: We aimed to establish a human lung tissue biobank of CDH and CPAM patients together with age-matched controls, coupled with a clinical database. METHODS: Pathology records from autopsies or surgical specimens for CDH and CPAM cases between 1980 and 2017 were reviewed. For surviving individuals, clinical patient data was obtained from corresponding pediatric surgery reports. Formalin-fixed, paraffin-embedded tissues of patients and age-matched controls were systematically stored for further translational studies. RNA integrity was determined on selected CDH blocks. RESULTS: A total of 16 CDH and 18 CPAM and age-matched control lung tissue blocks were included in our biobank. Ages ranged from 22 to 41 weeks of gestation (GA) in CDH (33.9 ±â€¯6.35 weeks) and 26 weeks (GA) and 12 years in CPAM (2.3 ±â€¯3.7 y). RNA isolation from CDH and control blocks yielded good RNA quality (OD 260/280 ratio: 2.01-2.09, OD 260/230 ratio: 2.04-2.09). CONCLUSION: We established a unique human biobank for CDH and CPAM tissues. The combination with clinical patient data will allow us to design future translational studies to improve our understanding of the disease pathogenesis of these congenital malformations.