Identification of biomarkers in animal models of progressive multiple sclerosis using RNA sequencing
| Project/Area Number |
17K15628
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | バイオインフォマティクス / 多変量解析 / ビッグデータ / バイオマーカー / 動物モデル / 進行型多発性硬化症 / 主成分分析 / 多発性硬化症 / 自己免疫 / トランスレーショナルリサーチ / 免疫学 |
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| Outline of Final Research Achievements |
We have established two murine models of progressive multiple sclerosis (MS) by sensitizing SJL/J and A.SW mice with myelin oligodendrocyte glycoprotein (MOG). Neuropathologically, SJL/J mice exhibit T cell infiltration in the central nervous system (CNS); A.SW mice develop CNS antibody deposition. In this study, using the two distinct progressive EAE models, we aimed to determine biomarkers contributing to the homogeneity and heterogeneity. Using principal component analysis (PCA) of CNS transcriptome data, we found the down-regulation of CNS prolactin in the two models. Pattern matching analysis of spleen transcriptome with CNS PCA showed 333 splenic surrogate markers including Stfa2l1, which reflected the changes in the CNS. Among the surrogate markers in the spleen, two genes (PER1/MIR6883 and FKBP5) and one gene (SLC16A1/MCT1) were also significantly up-regulated and down-regulated in human MS peripheral blood. This suggests that these genes may be biomarkers in progressive MS.
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| Academic Significance and Societal Importance of the Research Achievements |
多発性硬化症（MS）は病勢の違いにより進行型と再発寛解型に分類され，再発寛解型の多くの症例はのちに進行型へと移行する。再発寛解型MSの治療や病態の解明は進んでいるが，進行型MSの病態は不明な点が多く，治療薬の開発も遅れている。二つの病態の異なる進行型MS動物モデルを比較検討した研究は本研究が世界で初めてであり，両モデルの病勢進行に関与しているプロラクチンは治療薬の標的となり得ることを示唆した。また，二つの進行型MS動物モデルおよびヒト進行型MS患者において共通して増減する末梢バイオマーカー候補因子の探索を行った研究も極めて少なく，今後のMS臨床研究に新しい光明を投じる可能性を示唆した。
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Report
(4 results)
Research Products
(42 results)
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[Presentation] First national hepatitis B viral load testing in Nepal: Laboratory perspective for Nepalese national treatment guideline.2019
Author(s)
Sundar Khadka, 角田郁生, 尾村誠一, 佐藤文孝, 朴雅美, 藤田貢, 崎山奈美江, 中村優美和, 甲木蒼紫, Roshan Pandit, Subhash Dhital, Jagat Bahadur Baniya, Surendra Tiwari, Bimal Shrestha, Sanjeet Pandit, Mukunda Sharma, Shravan Kumar Mishra
Organizer
第67回日本ウイルス学会学術集会
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