Searching for mechanisms underlying lung and airway remodeling and mechano-sensing processes regulated by substrate stiffness.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09578
• 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: Aichi Medical University (2017-2018); Nagoya University (2016)
• Principal Investigator: Ito Satoru 愛知医科大学, 医学部, 准教授 (60378073)
• Research Collaborator: 浅野 周一 名古屋大学, 大学院医学系研究科, 大学院生 ; 高橋 光太 名古屋大学, 大学院医学系研究科, 大学院生 ; 宮沢 亜矢子 名古屋大学, 大学院医学系研究科, 大学院生
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: メカニカルストレス / リモデリング / 気管支喘息 / 肺線維症 / 肺線維芽細胞 / 肺癌 / 気道平滑筋 / メカノバイオロジー

Outline of Final Research Achievements

We investigated mechanisms underlying substrate stiffness regulates cellular functions.
In human lung fibroblasts, migration and differentiation to myofibroblasts were enhanced by stiff substrate.
Expression of PD-L1 and cell growth were affected by matrix stiffness in human lung cancer cells. It is suggested that stiffness as a tumor environment regulates PD-L1 expression, which leads to evasion of the immune system and tumor growth.　Activation of lung fibroblasts by the stiff lung and　positive feedback may be involved in the mechanisms of　progression of pulmonary fibrosis.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

細胞が足場として利用している基質の硬度を感知する基質力覚検知機構を明らかにし、肺や気道の線維化やリモデリングや病態や肺がんの免疫逃避機構の機序を解明することを目的として研究を行った。