Elucidation of immune cell activation mechanism in the cholinergic anti-inflammatory pathway
| Project/Area Number |
19K21297
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| Project/Area Number (Other) |
18H06192 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Inoue Tsuyoshi 東京大学, 医学部附属病院, 特任助教 (30821665)
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| Project Period (FY) |
2018-08-24 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腎臓 / 迷走神経刺激 / マクロファージ / 急性腎障害 |
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| Outline of Research at the Start |
炎症はさまざまな疾患の進展・増悪に深く関わっており，その制御は疾患の改善・予防に非常に重要である．最近の研究によって，神経系による免疫系の制御，なかでも迷走神経刺激を介した炎症の制御が，疾患の改善に寄与することが分かってきた．また，迷走神経刺激装置の臨床応用も関節リウマチや炎症性腸疾患などで進められている．そこで，本申請では，敗血症モデルおよび急性腎障害モデルを用いて，新規の抗炎症・臓器保護メカニズムの解明を目指す．
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| Outline of Final Research Achievements |
We investigated the mechanism regarding the renal protection effect of vagus nerve stimulation,. Stimulating the vagus nerve releases acetylcholine from the nerve endings, and we showed that acetylcholine induces Hes1 gene expression through a specific receptor present in macrophages and improves renal injury. We also found that in a model of cisplatin-induced kidney injury that is often encountered in clinical practice, vagus nerve stimulation can reduce renal damage even after kidney injury has occurred.
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| Academic Significance and Societal Importance of the Research Achievements |
多くの方が腎臓病を患う一方、腎臓病の根本的な治療法はいまだに存在せず、新たな治療法の開発は喫緊の課題である。本研究によって、神経系－免疫系を介した新規の腎臓保護作用メカニズムの一端を解明することができた。今後さらに研究を進めることで、腎臓病の新規の治療法開発につなげていきたい。
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells2020
Author(s)
Higashijima Y, Matsui Y, Shimamura T, Nakaki R, Nagai N, Tsutsumi S, Abe Y, Link VM, Osaka M, Yoshida M, Watanabe R, Tanaka T, Taguchi A, Miura M, Ruan X, Li G, Inoue T, Nangaku M, Kimura H, Furukawa T, Aburatani H, Wada Y, Ruan Y, Glass CK, Kanki Y
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Journal Title
The EMBO Journal
Volume: 39
Issue: 7
Pages: 1-1
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mitochondrial damage causes inflammation via cGAS-STING signaling in acute kidney injury2019
Author(s)
Hiroshi Maekawa, Tsuyoshi Inoue, haruki Ouchi, Tzu-Ming Jao, Reiko Inoue, Hiroshi Nishi, Rie Fujii, Fumiyoshi Ishidate, Tetsuhiro Tanaka, Yosuke Tanaka, Nobutaka Hirokawa, Masaomi Nangaku, Reiko Inagi
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Journal Title
Cell Reports
Volume: 29
Issue: 5
Pages: 1261-1273
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Non-canonical cholinergic anti-inflammatory pathway-mediated activation of peritoneal macrophages induces Hes1 and blocks ischemia/ reperfusion injury in the kidney.2019
Author(s)
Inoue T,Abe C, Kohro T, Tanaka S, Huang L, Yao J, Zheng S, Ye H, Inagi R, Stornetta RL, Rosin DL, Nangaku M, Wada Y, Okusa MD
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Journal Title
Kidney International
Volume: 95(3)
Issue: 3
Pages: 563-576
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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