Novel ARDS Therapy Targeting KIAA1462/JCAD

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08154
• 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: Kobe University
• Principal Investigator: Kobayashi Kazuyuki 神戸大学, 医学部附属病院, 特命教授 (50403275)
• Co-Investigator(Kenkyū-buntansha): 西村 善博 神戸大学, 医学部附属病院, 名誉教授 (20291453) ; 山本 正嗣 神戸大学, 医学部附属病院, 助教 (40542139) ; 永野 達也 神戸大学, 医学研究科, 講師 (80624684)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ARDS / KIAA1462 / JCAD

Outline of Final Research Achievements

Novel therapeutic agents and elucidation of the pathogenesis of ARDS, which still has a high mortality rate, are desired. In this study, we approached ARDS treatment from the perspective of both alveolar epithelial cells and vascular endothelial cells, focusing on inflammation and vascular permeability in pulmonary vascular endothelial cells, which are considered as important as alveolar and airway inflammation in the pathogenesis of ARDS.
A mouse model of LPS-induced lung injury was created, and it was confirmed that in KIAA1462 knockout (KO) mice, vascular intercellular adhesion was decreased and vascular permeability was increased, which exacerbated lung injury. In addition, qRT-PCR of lungs of mice after 24 hours of LPS administration showed that cytokines such as IL-6, TNF-α, IL-1β, CXCL-2, and MCP-1 were upregulated in KIAA1462 KO mice. Furthermore, we confirmed that the expression of VEcadherin, VCAM-1, and ICAM-1 was also decreased in KIAA1462 KO mice.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

ARDSにおけるJCAD/KIAA1462の関与、作用機序を示す論文はなく、本研究はJCAD/KIAA1462とARDSの直接的な関与を作用機序も含めて解析する世界で初めての研究となる。また、血管新生因子とARDSの病態を明らかにする極めて重要な研究課題であり、肺血管と肺胞壁構造を標的とした新規治療薬の開発につながる世界で初めての研究として位置づけられるとともに、重症COVID-19患者の救命につながる重要な研究であるといえる。