Identification of regulatory factors on airway epithelial barrier integrity and its clinical application for bronchial asthma

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591141
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nihon University
• Principal Investigator: GON Yasuhiro 日本大学, 医学部, 准教授 (80339316)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 気管支喘息 / 上皮バリア機能 / タイトジャンクション / 気道上皮細胞

Outline of Final Research Achievements

Airway epithelial barrier dysfunction plays an important role on the pathogenesis of bronchial asthma. To identify the regulatory molecules, we used an in vitro model using airway epithelial cells. We identified NDRG1 is involved in the regulation of airway epithelial barrier. We also found that mir-155 is important for the development of epithelial barrier. PCDH1 was recently identified as a susceptibility gene in asthma. PCDH1 was upregulated with the development of epithelial barrier function in cultured airway epithelial cells. PCDH1 gene knockdown disrupted both tight and adhesion junctions. Immunohistochemical analysis revealed strong PCDH1 expression in nasal and bronchial epithelial cells; however, expression decreased in inflamed tissues sampled from patients with CRS or bronchial asthma. These results suggest that PCDH1 is important for airway function as a physical barrier, and its dysfunction is involved in the pathogenesis of allergic airway inflammation.

Free Research Field

気管支喘息の病態研究