The role of myotubularins in pathogenesis of microscopic polyangiitis.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Akita University
• Principal Investigator: Kimura Hirotaka 秋田大学, 生体情報研究センター, 特任助教 (30382899)
• Co-Investigator(Renkei-kenkyūsha): Kofuji Satoshi 広島大学, 薬学部, 助教 (00508153) ; Sasaki Junko 秋田大学, 医学系研究科, 准教授 (30333371)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 顕微鏡的多発血管炎 / Myotubularin / イノシトールリン脂質

Outline of Final Research Achievements

Microscopic polyangiitis (MPA) is a necrotizing vasculitis affecting small vessels, resulting in alveolar hemorrhage and glomerulonephritis. An autoantibody, anti-neutrophilic cytoplasmic antibody (ANCA) is characteristically identified in MPA. In this study, we established a novel mouse model of MPA by administration of an extract from Candia yeast, histopathologically and serologically mimicking human disease. By utilizing this method, MPA was induced in neutrophil-specific myotubularins (MTMRs) deficient mice. Several genotypes among the MTMRs deficient mice exhibited increase of the levels of in vivo NETs and ANCA titers and exacerbation of histological damage. In the neutrophils, elevation of the levels of phosphatidylinositol 3-phoaphate, ROS generation and tolerance of Nets to DNase was observed. These results suggested that MTMRs might participate in pathogenesis of MPA through regulating neutrophil functions including NETs formation via phosphoinositide metabolism.

Free Research Field

医歯薬学