Analysis of the vascular protective genes identified by a newly established animal model of ANCA associated vasculitis.
| Project/Area Number |
18K07047
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小浦 美奈子 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 難治性疾患研究開発・支援センター, 主任研究員 (10370967)
伊藤 吹夕 帝京大学, 公私立大学の部局等, 助手 (20415079)
鈴木 治 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 難治性疾患研究開発・支援センター, 研究リーダー (70235935)
石神 昭人 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (50270658)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | MPO-ANCA / ANCA関連血管炎 / SCG/Kjマウス / NETs / Man-1 / SICMマウス / Quantitative trait loci / ANCA / 位置的候補遺伝子 / RNAシークエンス / 抗好中球細胞質自己抗体 / 自然発症マウス / SCG/Kj / 半月体形成性腎炎 / SICM |
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| Outline of Final Research Achievements |
Aberrant production of the anti-neutrophil cytosolic autoantibody (ANCA) causes the ANCA related vasculitis (AAV). To analyze the previously identified QTL on chromosome 1 for production of ANCA, we introduced the QTL to B6/lpr and proved the pathogenic function of the QTL (Autoimmunity 52:208, 2019). We identified two candidate genes for abnormal production of ANCA using the next generation sequencer. One was the structual gene for a proteinase inhibitor and it had non-synonymous polymorphisms. We produced recombinant proteins of wild and variant types to analyze their fuctional changes. Another one was the gene coding membrane surface protein on peripheral blood mononuclear cells.
We are going to develop these items into the medication experiment to animal individuals, and the surface character analysis of PBMC in a human AAV case. The results can possibly be the seeds for the development of therapautic medicines.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により得たタンパク、遺伝子欠損マウスを用いて、活性化顆粒球やNETsによる細胞傷害試験への影響、AAVモデルマウスへの治療的投与実験が可能となった。
折しも、新型コロナウイルス感染がパンデミックとなっており、感染者の急速かつ重篤な全身炎症が広く報告されている。この遺伝子が持つタンパク分解酵素阻害活性は、治療薬開発の糸口となる可能性がある。これらを発展させ、リード薬作製へつなげていきたい。
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Report
(5 results)
Research Products
(13 results)
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[Journal Article] Vasculitis and Crescentic Glomerulonephritis in a Newly Established Congenic Mouse Strain Derived From ANCA-associated Vasculitis-Prone SCG/Kj Mice2019
Author(s)
Yoshitomo Hamano, Fuyu Ito, Osamu Suzuki, Minako Koura, Shuji Matsuoka, Toshiyuki Kobayashi, Yoshinobu Sugitani, Nadila Wali, Ai Koyanagi, Okio Hino, Shoichi Suzuki, Ryuichi Sugamata, Hiromichi Yoshizawa, Wako Yumura, Naoki Maruyama, Yosuke Kameoka, Yoshihiro Noda, Yasuko Hasegawa, Tomio Arai, Kazuo Suzuki
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Journal Title
Autoimmunity
Volume: 52
Issue: 5-6
Pages: 208-219
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis.2019
Author(s)
Kameoka Y, Kishi F, Koura M, Yamakawa Y, Nagasawa R, Ito F, Matsuda J, Suzuki O, Nakayama T, Suzuki K
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Journal Title
Drug Des Devel Ther.
Volume: 13
Pages: 555-568
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Vasculitis and glomerulonephritis in a newly established congenic mice strain derived from ANCA-associated vasculitis-prone SCG/Kj mice2019
Author(s)
Yoshitomo Hamano, Fuyu Ito, Osamu Suzuki, Minako Koura, Shuji Matsuoka, Toshiyuki Kobayashi, Yoshinobu Sugitani, Nadila Wali, Okio Hino, Yosuke Kameoka, and Kazuo Suzuki
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Journal Title
Rheumatology
Volume: 58, suppl. 2
Pages: 76-76
Related Report
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[Journal Article] 肺結節性病変の中に小血管炎と著明な好酸球浸潤を認めたPR3-ANCA陽性の一例.2018
Author(s)
濱野 慶朋, 梶野 一徳, 林 大久生, 佐伯 春美, 松岡 周二, 小林 敏之, 杉谷 善信, 折茂 彰, 岸川 さつき, 荒川 敦, 樋野 興夫, 八尾 隆史.
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Journal Title
脈管学
Volume: 58
Pages: 36-36
Related Report
Peer Reviewed
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[Presentation] Vasculitis and Crescentic Glomerulonephritis in a Newly Established Congenic Mouse Strain Derived From ANCA-associated Vasculitis-Prone SCG/Kj Mice2019
Author(s)
Yoshitomo Hamano, Fuyu Ito, Osamu Suzuki, Minako Koura, Shuji Matsuoka, Toshiyuki Kobayashi, Yoshinobu Sugitani, Nadila Wali, Ai Koyanagi, Okio Hino, Shoichi Suzuki, Ryuichi Sugamata, Hiromichi Yoshizawa, Wako Yumura, Naoki Maruyama, Yosuke Kameoka, Yoshihiro Noda, Yasuko Hasegawa, Tomio Arai, Kazuo Suzuki
Organizer
International Vasculitis and ANCA Workshop
Related Report
Int'l Joint Research
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