Assay of autophagy-related diseases onset mechanisms with proteomic approach.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15664
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: The University of Tokushima
• Principal Investigator: INTOH Atsushi 徳島大学, 先端酵素学研究所(次世代), 助教 (70779058)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: プロテオミクス解析 / オートファジー / 細胞内小器官 / 炎症応答 / 生活習慣病

Outline of Final Research Achievements

Autophagy is a mechanism to digest damaged organelles, and serves an important role to maintain homeostasis of cells and organisms against many diseases. Extracellular proteins released in association with autophagy activity and organelle damages are candidates for the autophagy-related disease biomarkers. In this research, mouse proteomic analyses of released/secreted proteins from immunocompetent cells were performed with or without irritant particle stimulus. By this assay, many biomarker candidates were identified, and some of them are revealed to detect in blood serum and urine from autophagy-disease model mouse. Knock-down assay of the extracellular proteins also showed one of the identified protein negatively control the production of inflammatory cytokines, suggesting the identified protein is expected as a drug target.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

オートファジーは損傷した細胞内小器官を選択的に分解し、細胞の恒常性を維持する機構であり、この働きが弱まると神経変性疾患や炎症性疾患などが引き起こされることが知られている。このオートファジー不全からの疾患発症過程において細胞外レベルが顕著に変動するタンパク質は機能的な重要性だけでなく、関連疾患群の有効なバイオマーカーとなり得る。
本研究で明らかにした、刺激性微粒子による細胞小器官の損傷に伴って細胞外へ放出される因子群は、細胞や生体が有する恒常性維持機構の分子機構の解明だけでなく、血中や尿中から安易に採取できる疾患バイオマーカーとしての有効性も期待される。