Molecular mechanisms on how alveolar epithelial cells respond to exogenous stress in COPD

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Fujino Naoya 東北大学, 大学病院, 助教 (10633670)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 慢性閉塞性肺疾患 / 肺胞上皮細胞 / 組織幹細胞

Outline of Final Research Achievements

Chronic Obstructive Pulmonary Disease (COPD) is an intractable respiratory disease that causes progressive airflow limitation due to the destruction of airways and alveolar structures caused by long-term inhalation of toxic substances, mainly tobacco smoke. In this study, we isolated alveolar epithelial type II cells (type II cells), which are known as stem cells of alveolar epithelial cells, and aimed to establish a three-dimensional culture system. A co-culture system with fibroblasts was performed, and the sphere-forming ability of type II cells was improved by the use of a Rho kinase inhibitor. Immunohistochemical studies were performed using healthy and COPD lung tissue, and the percentage of stem cell type II cells was decreased in COPD lung tissue.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究の独自性は、新規開発したヒト肺組織細胞分離法を用い、これまで明らかにされていなかったヒト疾患肺組織におけるII型細胞の幹細胞性維持機構を分子レベルで解明できることが期待される点にある。さらに、II型細胞と線維芽細胞との共培養や、遺伝子発現解析を通して、COPD病態における多様な肺細胞ネットワークの一部が解明され、これまでの研究とは次元の違う精度の機能解析が期待される。