Reinforcement of colonic epithelial barrier via mAChR
Project/Area Number |
18K06946
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49010:Pathological biochemistry-related
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Research Institution | Asahikawa Medical College |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
矢澤 隆志 旭川医科大学, 医学部, 講師 (00334813)
加藤 剛志 旭川医科大学, 医学部, 准教授 (60194833)
宇和田 淳介 旭川医科大学, 医学部, 助教 (70580314)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | TNF / MAP kinase / p38 / ADM17 / STIM1 / SOCE / ADAM17 / 炎症性腸疾患 / ムスカリン受容体 / TNF-α / 腸上皮バリア / TACE |
Outline of Final Research Achievements |
In intestinal epithelial cells, store-operated calcium entry (SOCE) following muscarinic M3 receptor activation positively regulates p38MAP kinase and activates the protease ADAM17 to cleave/solubilize TNF-α. It was thought that it blocked the pathway and suppressed the spread of inflammation. In the course of this study, we found PNU-120596 as a substance that inhibits p38MAP kinase. Although this substance is widely used as a positive allosteric modulator of α7 nAChR, it binds directly to p38MAP kinase and exerts an inhibitory effect without mediating α7 nAChR.
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Academic Significance and Societal Importance of the Research Achievements |
腸上皮バリアが破綻すると外来抗原や微生物が侵入し、マクロファージなどの免疫細胞が遊走浸潤して対抗し、TNF-αをはじめとする炎症促進因子を放出して腸上皮バリア機能をさらに低下させるという悪循環が生じ、このことは炎症性腸疾患の病態との関わりが深い。我々の研究成果はムスカリン受容体刺激がTNF-α converting enzyme(TACE)を活性化してTNF-α受容体(TNFR)の密度を低下させると同時に、その可溶化された断片(sTNFR)がTNF-α自体を中和してTNF-α経路を抑制していることを示し、炎症性腸疾患の新しい治療法の可能性を示したものである。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] β-Hydroxybutyrate enhances the cytotoxic effect of cisplatin via the inhibition of HDAC/survivin axis in human hepatocellular carcinoma cell2020
Author(s)
Daisuke Mikami, Mamiko Kobayashi, Junsuke Uwada, Takashi Yazawa, Kazuko Kamiyama, Kazuhisa Nishimori, Yudai Nishikawa, Sho Nishikawa, Seiji Yokoi, Takanobu Taniguchi, and Masayuki Iwano
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Journal Title
Journal of Pharmacological Sciences
Volume: 142
Pages: 1-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Cyclooxygenase‐2 is acutely induced by CCAAT/enhancer‐binding protein β to produce prostaglandin E2 and F2α following gonadotropin stimulation in Leydig cells2019
Author(s)
Takashi Yazawa,Yoshitaka Imamichi,Koh‐ichi Yuhki,Junsuke Uwada, Daisuke Mikami,Masayuki Shimada,Kaoru Miyamoto,Takeshi Kitano, Satoru Takahashi,Toshio Sekiguchi,Nobuo Suzuki,Md. Rafiqul Islam Khan,Fumitaka Ushikubi, Akihiro Umezawa, Takanobu Taniguchi
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Journal Title
Mol Reprod Dev
Volume: 86
Pages: 786-779
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] β-Hydroxybutyrate, a ketone body, reduces the cytotoxic effect of cisplatin via activation of HDAC5 in human renal cortical epithelial cells2019
Author(s)
Daisuke Mikami,Mamiko Kobayashi,Junsuke Uwada TakashiYazawa,Kazuko Kamiyama,Kazuhisa Nishimori,Yudai Nishikawa,Yukie Morikawa,Seiji Yokoi,Naoki Takahashi,Kenji Kasuno,Takanobu Taniguchi,Masayuki Iwano
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Journal Title
Life Sciences
Volume: 222
Pages: 125-132
DOI
Related Report
Peer Reviewed
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[Journal Article] β-Hydroxybutyrate, a ketone body, reduces the cytotoxic effect of cisplatin via activation of HDAC5 in human renal cortical epithelial cells.2019
Author(s)
Mikami D, Kobayashi M, Uwada J, Yazawa T, Kamiyama K, Nishimori K, Nishikawa Y, Morikawa Y, Yokoi S, Takahashi N, Kasuno K, Taniguchi T, Iwano M.
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Journal Title
Life Sciences
Volume: 222
Pages: 125-132
DOI
Related Report
Peer Reviewed / Open Access
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