Alterations at the Synthesis and Degradation of E-cadherin in the Human Lungs with Emphysema

Abstract

Pulmonary emphysema leads to a cascade of events starting with enlarged alveoli, loss of alveoli and, subsequently to the damage and disruption of pulmonary epithelium. The integrity of the pulmonary epithelium, which is constituted by pneumocytes linked to each other through E-cadherin proteins, is important for respiration. The aim of the present study was to detect the content and destruction of E-cadherin protein and to investigate the contribution of E-cadherin to pulmonary emphysema pathogenesis. The structural changes, reparative capacity of the pulmonary epithelium, amount of E-cadherin protein and, the immunoreactivity of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9) were evaluated in emphysematous (n=7) and non-emphysematous (n=6) areas of lung samples taken from patients with chronic obstructive pulmonary disease. Emphysematous areas are characterized by enlarged alveoli, disrupted alveolar walls and epithelium, increased type 2 pneumocytes and NEDD9 immunoreactivity, and reduced E-cadherin proteins. Our data shows that E-cadherin levels are decreased in emphysematous areas due to its degradation by NEDD9. Decreased E-cadherin levels also lead to the disintegration of the pulmonary epithelium by causing the presence of weakness intercellular connections or the absence of intercellular connections. The repair of the pulmonary epithelium could not complete due to the reduced E-cadherin, because type 2 pneumocytes could not differentiate into type 1 pneumocytes. In conclusion, the reduced E-cadherin levels lead to emphysematous alterations in human lungs and contributes to pulmonary emphysema pathogenesis.