Development of foundation for ARDS treatment based on controlling vascular permeability

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17217
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Oita University
• Principal Investigator: Akamine Takahiro 大分大学, 医学部, 助教 (60799435)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ARDS / 血管透過性 / ROCK

Outline of Final Research Achievements

ARDS is a disease with a poor prognosis and a high mortality rate. This caused by leakage of blood components in lung cells due to increased vascular permeability due to vascular endothelial cell damage of lung. Increased vascular permeability originally contributes to the extravasation of immune cells and plasma components as a protective response against inflammation, but excessive increase is closely related to the pathology of various diseases. The results of this study revealed that ROCK1/2 conditional knockout (ROCK DcKO) mice have enhanced pulmonary vascular permeability. In the lung tissue of ROCK DcKO mice, the intensity of phalloidin staining and VE-cadherin staining was obviously reduced. Thus, our study suggest ROCK might be involved in maintenance of lung homeostasis though actin cytoskeleton rearrangement.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

非心原性肺水腫をはじめとして、血管透過性亢進による組織の恒常性破錠は生体にとって重篤な状況を引き起こす。本研究による血管透過性亢進に関わる分子機序の解明はARDSなどの血管透過性亢進が惹起される病態の理解の深化に資することが期待される。また、これまでのROCKに関する多くの研究は培養細胞と特異的なキナーゼ活性阻害薬が用いられてきた。しかし、中にはROCKのリン酸化基質が明確でなく、分子機序の説明が不完全な反応も多く存在する。本課題の完遂はこれまで不完全であった分子機序に対してより明確な解答を与えることが期待される。