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

Year 2017, , 61 - 68, 27.12.2017

Ecem Gogus Ozgecan Kayalar H. Gul Ongen Fusun Oztay

https://doi.org/10.5152/EurJBiol.2017.1711

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.

Keywords

Pulmonary emphysema, COPD, E-cadherin, pulmonary epithelium

References

• 1. Kim V, Rogers TJ, Criner GJ. New concepts in the pathobiology of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008; 5(4): 478-85. 2. Sharafkhaneh A, Hanania NA, Kim V. Pathogenesis of emphysema: from the bench to the bedside. Proc Am Thorac Soc 2008; 5: 475-7. 3. Brusselle GG, Bracke KR, Maes T, D’hulst AI, Moerloose KB, Joos GF, et al. Murine models of COPD. Pulm Pharmacol Ther 2005; 19(3): 155-65. 4. Besiktepe N, Kayalar O, Ersen E, Oztay F. The copper dependent-lysyl oxidases contribute to the pathogenesis of pulmonary emphysema in chronic obstructive pulmonary disease patients. J Trace Elem Med Biol 2017; 44: 247-55. 5. Li XY, Rahman I, Donaldson K, MacNee W. Mechanisms of cigarette smoke induced increased airspace permeability. Thorax 1996; 51(5): 465-71. 6. Baraldo S, TuratoG, Saetta M. Pathophysiology of the small airways in chronic obstructive pulmonary disease. Respiration 2012; 84(2): 89-97. 7. Henson PM, Vandivier RW, Douglas IS. Cell Death, remodeling, and repair in chronic obstructive pulmonary disease? Proc Am Thorac Soc 2006; 3(8): 713-7. 8. Man Y, Hart VJ, Ring CJ, Sanjar S, West MR. Loss of epithelial integrity resulting from E-cadherin dysfunction predisposes airway epithelial cells to adenoviral infection. Am J Respir Cell Mol Biol 2000; 23(5): 610-7. 9. Oldenburger A, Poppinga WJ, Kos F, de Bruin HG, Rijks WF, Heijink IH, et al. A-kinase anchoring proteins contribute to loss of E-cadherin and bronchial epithelial barrier by cigarette smoke. Am J Physiol Cell Physiol 2014; 306(6): C585-97. 10. Liguori G, Pavone LM, Assisi L, Langella E, Tafuri S, Mirabella N, et al. Expression of orexin B and its receptor 2 in rat testis. Gen Comp Endocrinol 2017; 242: 66-73. 11. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54. 12. Needham M, Stockley RA. α1-Antitrypsin deficiency? Clinical manifestations and natural history. Thorax 2004; 59(5): 441-5. 13. Emam M, Renaud JF, Gharbi N. Characterization of lung’s emphysema distribution: Numerical assessment of disease development, establishment, maintenance, and remodeling. J Cell Biol 2010; 6: 907-17. 14. Shapiro SD. Animal models for chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2000; 22(1): 4-7. 15. Bals R. Alpha-1-antitrypsin deficiency. Best Pract Res Clin Gastroenterol 2010; 24(5): 629-33. 16. Heijink IH, Brandenburg SM, Noordhoek JA, Postma DS, Slebos DJ, Oosterhout AJ. Characterization of cell adhesion in airway epithelial cell types using electric cell–substrate impedance sensing. Eur Respir J 2010; 35(4): 894-903. 17. Shaykhiev R, Otaki F, Bonsu P, Dang DT, Teater M, Strulovici-Barel Y, et al. Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo. Cell Mol Life Sci 2011; 68(5): 877-92. 18. Aggarwal NR, Chau E, Garibaldi BT, Mock JR, Susan T, Rao K, et al. Aquaporin 5 regulates cigarette smoke induced emphysema by modulating barrier and immune properties of the epithelium. Tissue Barriers 2013; 1(4): e25248. 19. Boxio R, Wartelle J, Nawrocki-Raby B, Lagrange B, Malleret L, Hirche T, et al. Neutrophil elastase cleaves epithelial cadherin in acutely injured lung epithelium. Respir Res 2016; 17(1): 129. 20. Chang JX, Gao F, Zhao GO, Zhang GJ. Expression and clinical significance of NEDD9 in lung tissues. Med Oncol 2012; 29(4): 2654-60. 21. Jin Y, Li F, Zheng C, Wang Y, Fang Z, Guo C, et al. NEDD9 promotes lung cancer metastasis through epithelial-mesenchymal transition. Int J Cancer 2014; 134(10): 2294-304. 22. Tikhmyanova N, Golemis EA. NEDD9 and BCAR1 negatively regulate E-cadherin membrane localization, and promote E-cadherin degradation. PLoS One 2011; 6(7): e22102. 23. Mohamet L, Hawkins K, Ward CM. Loss of function of E-Cadherin in embryonic stem cells and the relevance to models of tumorigenesis. J Oncol 2011; 2011: 352616. 24. Kayalar O, Oztay F. Retinoic acid induced repair in the lung of adult hyperoxic mice, reducing transforming growth factor-beta1 mediated abnormal alterations. Acta Histochem 2014; 116(5): 8109. 25 Nagaoka K, Zhang H, Watanabe G, Taya K. Epithelial cell differentiation regulated by MicroRNA-200a in mammary glands. PLoS One 2013; 8(6): e65127. 26. Martorana PA, Cavarra E, Lucattelli M, Lungarella G. Models for COPD involving cigarette smoke. Drug Discov Today Dis Models 2006; 3(3): 225-30.