Dysregulation of E-cadherin in pulmonary cell damage related with COPD contributes to emphysema.

Air pollution, especially at chronic exposure to high concentrations, is a respiratory risk factor for the development of chronic obstructive pulmonary disease (COPD). E-cadherin, a cell-cell adhesion protein, is involved in the integrity of the alveolar epithelium. Causes of E-cadherin decreases in emphysematous areas with pulmonary cell damage related to COPD are not well understood. We aimed to determine the molecules causing the decrease of E-cadherin and interactions between these molecules. In emphysematous and non-emphysematous areas of lungs from COPD patients (n = 35), levels of E-cadherin, HDACs, Snail, Zeb1, active-β-catenin, p120ctn, and Kaiso were determined by using Western Blot. The interactions of HDAC1, HDAC2, and p120ctn with transcription co-activators and Kaiso were examined by co-immunoprecipitation experiments. The methylation status of the CDH1 promoter was investigated. E-cadherin, Zeb1, Kaiso, and active-β-catenin were decreased in emphysema, while HDAC1, HDAC2, and p120ctn2 were increased. Snail, Zeb1, Twist, active-β-catenin, Kaiso, and p120ctn co-precipitated with HDAC1 and HDAC2. E-cadherin, Kaiso, and active-β-catenin co-precipitated with p120ctn. HDAC1-Snail and HDAC2-Kaiso interactions were increased in emphysema, but p120ctn-E-cadherin interaction was decreased. The results show that HDAC1-Snail and HDAC2-Kaiso interactions are capable of decreasing the E-cadherin in emphysema. The decreased interaction of p120ctn/E-cadherin leads to E-cadherin destruction. The decreased E-cadherin and its induced degradation in pneumocytes cause impaired repair and disintegrity of the epithelium. Approaches to suppress HDAC1-Snail and HDAC2-Kaiso interactions may help the protection of alveolar epithelial integrity by increasing the E-cadherin stability in pneumocytes.