2022 Fiscal Year Final Research Report
Development of blood novel biomarkers and therapy for multiple sclerosis by using glial connexin-expressing exosome
| Project/Area Number |
20K22910
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
Maimaitijiang Guzailiayi 国際医療福祉大学, トランスレーショナルニューロサイエンスセンター, 特任助教 (60887107)
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| Project Period (FY) |
2020-09-11 – 2023-03-31
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| Keywords | 脱髄疾患 / 多発性硬化症 / エキソソーム / コネキシン / グリア線維性蛋白 / イソフォーム / アストログリア / マイクロRNA |
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| Outline of Final Research Achievements |
Serum exosome (Ex) connexin (Cx) isoforms were analyzed in multiple sclerosis (MS). MS patients had significantly greater Ex glial fibrillary acidic protein amounts than HC. Ex GJA1-29k was higher in MS than healthy controls (HC). In MS, 29k was highest in secondary progression (SP)>remission>relapse>HC (p<0.001). Wild type (WT) mice showed increase of Ex GJA1-29k upon EAE compared with the pre-immunized state; more pronounced in chronic than acute phase. By contrast, asroglia-specific Cx43 inducible conditional knockout (icKO) mice showed attenuated acute and chronic EAE compared with WT mice, and had no and attenuated increase of 29k at acute and chronic phases, respectively. Splenic regulatory T cells and IL10 production were significantly greater in Cx43 icKO than WT mice upon EAE. Increased circulating Ex GJA1-29k, partly derived from astroglia, is associated with SPMS reflecting progressive astrogliosis, and may propagate pro-inflammatory messages via bound microRNA.
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| Free Research Field |
神経内科学
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| Academic Significance and Societal Importance of the Research Achievements |
多発性硬化症で二次進行期が起こる理由は不明で、二次進行期バイオマーカーもない。本研究で、MSでは二次進行期に血清中のグリア線維性蛋白とコネキシン低分子量イソフォームGJA1-29kを含有するエキソソームが著増することを発見した。これらの血清エキソソームは、多発性硬化症の新たな二次進行期バイオマーカーとなることが期待され、病期の診断において大きな意義を有する。野生型と脳アストログリア特異的なコネキシン43のinducibel conditional knockoutマウスの実験的脳脊髄炎の比較から、GJA1-29kを含有するエキソソームがアストログリア由来のものが多いことを証明できた。
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