Molecular biology of the mechanism of tobacco-induced reduction of lung barrier function based on HIF-1 activity analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09210
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Kansai Medical University
• Principal Investigator: NISHI Kenichiro 関西医科大学, 医学部, 研究員 (50340716)
• Co-Investigator(Kenkyū-buntansha): 広田 喜一 関西医科大学, 医学部, 研究員 (00283606)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 喫煙 / タバコ / タバコ抽出液 / 肺胞上皮 / 肺血管内皮 / 細胞間バリア

Outline of Final Research Achievements

We developed a system to measure the vascular permeability of intercellular barriers in this study and confirmed that the permeability can be quantified using the fluorescent substance FITC-dextran as an indicator. Vascular permeability was observed to be altered by lipopolysaccharide (LPS) treatment, HIF activation (hypoxic environment and use of HIF-PH inhibitors) and cigarette smoke extract (CSE) conditioning. Next-generation sequencing techniques confirmed that these treatments affect gene expression in human pulmonary microvascular endothelial cells (HPMECs), particularly the expression of intercellular adhesion molecules. From these results, we conclude that CSE increases the permeability of the intercellular barrier via HIF.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

タバコ-バリア機能の低下、HIF-1-バリア機能の低下という現象同士をつなぎ、タバコ-HIF-1-バリア機能の低下という関係が存在することを主に肺胞上皮、肺血管内皮のバリア機能を標的に研究することが本研究の具体的な目的であった。この過程でシグナル伝達を改変することでタバコ-バリア機能の低下という関連を切断する端緒をつかむ事も本研究の要素であり、本研究成果は報告者らの今までの研究成果に立脚した独自性の高いものである。