The elucidation of the World of AhR in the intestinal environment ,followed by the diverse clinical applications.
Project/Area Number |
18KK0246
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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Research Institution | Keio University |
Principal Investigator |
KANAI Takanori 慶應義塾大学, 医学部(信濃町), 教授 (40245478)
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Co-Investigator(Kenkyū-buntansha) |
長沼 誠 慶應義塾大学, 医学部(信濃町), 客員教授 (00265810)
杉本 真也 慶應義塾大学, 医学部(信濃町), 助教 (20626387)
寺谷 俊昭 慶應義塾大学, 医学部(信濃町), 講師 (40624408)
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Project Period (FY) |
2019-02-07 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
|
Keywords | 青黛 / インジゴ類 / 潰瘍性大腸炎(UC) / AhRコンディショナルノックアウトマウス / 腸内細菌叢 / 腸管微小循環 / メタゲノム解析 / 腸内細菌 |
Outline of Final Research Achievements |
We found homology between changes in the intestinal microbiota of indigo naturalis(IN)-fed mice and patients with UC after the IN treatment. Next, we demonstrated that IN and indigo induced pulmonary arterial hypertension via the AhR-passway by using a rat model, which was published in the paper. In addition, we analyzed the changes in immune cells, epithelial cells, and intestinal microflora using conditional knockout mice, in which AhR is specifically deleted by tamoxifen administration in the specific cells, and this content is currently being submitted for publication.
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Academic Significance and Societal Importance of the Research Achievements |
我々が有する青黛使用歴のあるUC患者の世界で唯一の貴重なデータベースを活用し、特に主成分のAhRリガンドであるインジゴ類に注目し、多方面からアプローチすることにより、日本発のシーズを世界へ発信する。現在の難治性UC患者の福祉に資するのみならず、医療資源の大幅な削減、UCの病態理解につなげることが、UCへの青黛効果の実証を主導してきた我々の使命と考え、本研究の着想に至った。このような研究戦略により、従来の基礎医学的なアプローチとは異なる、効率的な基礎臨床一体型研究を迅速に展開できると考える。
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Report
(4 results)
Research Products
(80 results)
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[Journal Article] Characteristics of the Mucosal Surface on Scanning Electron Microscopy in Patients with Remitting Ulcerative Colitis2021
Author(s)
Nomura E, Sujino T, Hosoe N, Yoshimatsu Y, Tanemoto S, Takabayashi K, Mutaguchi M, Shimoda M, Naganuma M, Ogata H, Kanai T.
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Journal Title
Dig Dis Sci.
Volume: -
Issue: 9
Pages: 1-6
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Adrenomedullin for steroid-resistant ulcerative colitis: a randomized, double-blind, placebo-controlled phase-2a clinical trial.2021
Author(s)
Kita T, Ashizuka S, Ohmiya N, Yamamoto T, Kanai T, Motoya S, Hirai F, Nakase H, Moriyama T, Nakamura M, Suzuki Y, Kanmura S, Kobayashi T, Ohi H, Nozaki R, Mitsuyama K, Yamamoto S, Inatsu H, Watanabe K, Hibi T, Kitamura K.
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Journal Title
J Gastroenterol
Volume: 56
Issue: 2
Pages: 147-157
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pulmonary Arterial Hypertension Caused by AhR Signal Activation Protecting against Colitis.2021
Author(s)
Hiraide T., Teratani T., Uemura S., Yoshimatsu Y., Naganuma M., Shinya Y., Momoi M., Kobayashi E., Hakamata Y., Fukuda K., Kanai T., Kataoka M.
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Journal Title
Am J Respir Crit Care Med
Volume: 203
Issue: 3
Pages: 385-388
DOI
Related Report
Peer Reviewed
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[Journal Article] Phase 1 study on the safety and efficacy of E6011, antifractalkine antibody, in patients with Crohn's disease.2021
Author(s)
Matsuoka K., Naganuma M., Hibi T., Tsubouchi H., Oketani K., Katsurabara T., Hojo S., Takenaka O., Kawano T., Imai T., Kanai T.
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Journal Title
J Gastroenterol Hepatol
Volume: -
Issue: 8
Pages: 2180-2186
DOI
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Peer Reviewed / Open Access
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[Journal Article] An organoid-based organ-repurposing approach to treat short bowel syndrome2021
Author(s)
Sugimoto S, Kobayashi E, Fujii M, Ohta Y, Arai K, Matano M, Ishikawa K, Miyamoto K, Toshimitsu K, Takahashi S, Nanki K, Hakamata Y, Kanai T, Sato T.
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Journal Title
Nature
Volume: 592
Pages: 99-104
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mucosal concentrations of N-acetyl-5-aminosalicylic acid is related to endoscopic activity in ulcerative colitis patients with mesalamine.2020
Author(s)
Fukuda T, Naganuma M, Takabayashi K, Hagihara Y, Tanemoto S, Nomura E, Yoshimatsu Y, Sugimoto S, Nanki K, Mizuno S, Mikami Y, Fukuhara K, Sujino T, Mutaguchi M, Inoue N, Ogata H, Iwao Y, Abe T, Kanai T.
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Journal Title
J Gastroenterol Hepatol.
Volume: 35
Issue: 11
Pages: 1878-1885
DOI
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Peer Reviewed / Open Access
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[Journal Article] The liver-brain-gut neural arc maintains the Treg cell niche in the gut2020
Author(s)
Teratani T, Mikami Y, Nakamoto N, Suzuki T, Harada Y, Okabayashi K, Hagihara Y, Taniki N, Kohno K, Sibata S, Miyamoto K, Ishigame H, Chu Po-Sung, Sujino T, Suda W, Hattori M, Matsui M, Okada T, Okano H, Inoue M, Yada T, Kitagawa Y, Yoshimura A, Tanida M, Tsuda M, Iwasaki Y, Kanai T.
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Journal Title
Nature
Volume: 585
Issue: 7826
Pages: 591-596
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Angiopoietin-like protein 4 deficiency augments liver fibrosis in liver diseases such as nonalcoholic steatohepatitis in mice through enhanced free cholesterol accumulation in hepatic stellate cells.2020
Author(s)
Teratani T., Tomita K., Wada A., Sugihara N., Higashiyama M., Inaba K., Horiuchi K., Hanawa Y., Nishii S., Mizoguchi A., Tanemoto R., Ito S., Okada Y., Kurihara C., Akita Y., Narimatsu K., Watanabe C., Komoto S., Oike Y., Miura S., Hokari R., Kanai T.
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Journal Title
Hepatol Res
Volume: -
Issue: 5
Pages: 580-592
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Peer Reviewed / Open Access
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[Journal Article] Chromosome Engineering of Human Colon-Derived Organoids to Develop a Model of Traditional Serrated Adenoma.2020
Author(s)
Kawasaki K, Fujii M, Sugimoto S, Ishikawa K, Matano M, Ohta Y, Toshimitsu K, Takahashi S, Hosoe N, Sekine S, Kanai T, Sato T.
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Journal Title
Gastroenterology
Volume: 3
Issue: 3
Pages: 638-651
DOI
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Peer Reviewed / Open Access
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[Journal Article] Indigo naturalis is effective even in treatment-refractory patients with ulcerative colitis: a post hoc analysis from the INDIGO study.2020
Author(s)
Naganuma M, Sugimoto S, Fukuda T, Mitsuyama K, Kobayashi T, Yoshimura N, Ohi H, Tanaka S, Andoh A, Ohmiya N, Saigusa K, Yamamoto T, Morohoshi Y, Ichikawa H, Matsuoka K, Hisamatsu T, Watanabe K, Mizuno S, Abe T, Suzuki Y, Kanai T; INDIGO Study Group.
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Journal Title
J Gastroenterol.
Volume: 55
Issue: 2
Pages: 169-180
DOI
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Peer Reviewed / Open Access
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[Journal Article] Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter randomised controlled trial.2020
Author(s)
Naganuma M, Yokoyama Y, Motoya S, Watanabe K, Sawada K, Hirai F, Yamamoto T, Hanai H, Omori T, Kanai T, Hibi T
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Journal Title
J Gastroenterol
Volume: 4
Issue: 4
Pages: 390-400
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of vedolizumab in Japanese patients with Crohn's disease: a prospective, multicenter, randomized, placebo-controlled Phase 3 trial with exploratory analyses.2020
Author(s)
Watanabe K, Motoya S, Ogata H, Kanai T, Matsui T, Suzuki Y, Shikamura M, Sugiura K, Oda K, Hori T, Araki T, Watanabe M, Hibi T.
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Journal Title
J Gastroenterol
Volume: 3
Issue: 3
Pages: 291-306
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Somatic inflammatory gene mutations in human ulcerative colitis epithelium.2020
Author(s)
Nanki K, Fujii M, Shimokawa M, Matano M, Nishikori S, Date S, Takano A, Toshimitsu K, Ohta Y, Takahashi S, Sugimoto S, Ishimaru K, Kawasaki K, Nagai Y, Ishii R, Yoshida K, Sasaki N, Hibi T, Ishihara S, Kanai T, Sato T.
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Journal Title
Nature
Volume: 7789
Issue: 7789
Pages: 254-259
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Significance of Conducting 2 Types of Fecal Tests in Patients with Ulcerative Colitis.2019
Author(s)
Naganuma M, Kobayashi T, Nasuno M, Motoya S, Kato S, Matsuoka K, Hokari R, Watanabe C, Sakamoto H, Yamamoto H, Sasaki M, Watanabe K, Iijima H, Endo Y, Ichikawa H, Ozeki K, Tanida S, Ueno N, Fujiya M, Sako M, Takeuchi K, Sugimoto S, Abe T, Hibi T, Suzuki Y, Kanai T.
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Journal Title
Clin Gastroenterol Hepatol
Volume: 19
Issue: 5
Pages: 30843-2
DOI
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Peer Reviewed / Open Access
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[Journal Article] Efficacy of Therapeutic Intervention for Patients With an Ulcerati Colitis Mayo Endoscopic Score of 12019
Author(s)
Fukuda T, Naganuma M, Sugimoto S, Ono K, Nanki K, Mizuno S, Kimura K, Mutaguchi M, Nakazato Y, Takabayashi K, Inoue N, Ogata H, Iwao Y, Kanai T.
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Journal Title
Inflamm Bowel Dis
Volume: 25
Issue: 4
Pages: 782-788
DOI
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Peer Reviewed / Open Access
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[Journal Article] Concerns and side effects of azathioprine during adalimumab induction and maintenance therapy for Japanese patients with Crohn's disease: a sub-analysis of a prospective randomized clinical trial (DIAMOND study).2019
Author(s)
Hisamatsu T, Matsumoto T, Watanabe K,;Nakase H, Motoya S, Yoshimura N, Ishida T, Kato S, Nakagawa T, Esaki M, Nagahori M, Matsui T, Naito Y, Kanai T, Suzuki Y, Nojima M, Watanabe M, Hibi T; DIAMOND study group.
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Journal Title
J Crohns Colitis.
Volume: 印刷中
Issue: 9
Pages: 1097-1104
DOI
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Peer Reviewed / Open Access
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[Journal Article] Middle-term prognosis in patients with ulcerative colitis who achieved clinical and endoscopic remission by budesonide rectal foam.2019
Author(s)
Naganuma M, Hirai F, Kobayashi K, Watanabe K, Takeuchi K, Aoyama N, Nozawa H, Motoya S, Ohmori T, Harada A, Nagai Y, Abe T, Yamada Y, Inagaki K, Shimizu N, Kanai T, Watanabe M.
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Journal Title
PLoS One
Volume: 14
Issue: 8
Pages: e0220413-e0220413
DOI
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Peer Reviewed / Open Access
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[Journal Article] Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey2019
Author(s)
Naganuma M, Sugioto S, Suzuki H, Matsuno Y, Araki T, Shimizu H, Hayashi R, Fukuda T, Nakamoto N, Iijima H, Nakamura S, Kataoka M, Tamura Y, Tatsumi K, Hibi T, Suzuki Y, Kani T, INDIGO survey Group
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Journal Title
J Gastroenterol
Volume: 54(10)
Issue: 10
Pages: 891-896
DOI
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Peer Reviewed / Open Access
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[Journal Article] Toll-Like Receptor 7 Agonist-Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells.2018
Author(s)
Kiyohara H, Sujino T, Teratani T, Miyamoto K, Arai MM, Nomura E, Harada Y, Aoki R, Koda Y, Mikami Y, Mizuno S, Naganuma M, Hisamatsu T, Kanai T.
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Journal Title
Cell Mol Gastroenterol Hepatol.
Volume: 7
Issue: 1
Pages: 135-156
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Peer Reviewed / Open Access
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[Presentation] 内視鏡診断が有用であったCampylobacter腸炎併発の難治性潰瘍性大腸炎の一例.2020
Author(s)
古島 雅子, 清原 裕貴, 高林 馨, 島田 史恵, 春日 良介, 三上 洋平, 河口 貴昭, 南木 康作, 筋野 智久, 牟田口 真, 細江 直樹, 緒方 晴彦, 金井 隆典.
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第361回 日本消化器病学会 関東支部例会
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[Presentation] 難治性潰瘍性大腸炎に対するシクロスポリン持続静注療法の使用意義.2020
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青木 康浩, 福田 知広, 吉松 裕介, 南木 康作, 三上 洋平, 福原 佳代子, 牟田口 真, 筋野 智久, 高林 馨, 井上 詠, 緒方 晴彦, 岩男 泰, 長沼 誠, 金井 隆典.
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第28回日本消化器関連学会週間
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[Presentation] 発赤領域として発見されESDにより確定診断されたUC関連平坦型dysplasiaの1例.2020
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萩原 裕也, 岩男 泰, 牟田口 真, 杉本 真也, 南木 康作, 三上 洋平, 筋野 智久, 前畑 忠輝, 矢作 直久, 下田 将之, 長沼 誠, 緒方 晴彦, 金井 隆典.
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第38回日本大腸検査学会総会
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[Presentation] ニボルマブ投与中に急性腸炎を発症した一例2019
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佐藤萌, 脇坂悠介, 津軽開, 平田賢郎, 三上洋平, 水野慎大, 筋野智久, 須河恭敬, 浜本康夫, 高石官均, 長沼誠, 金井隆典, 前原純樹
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[Presentation] 潰瘍性大腸炎患者に対する青黛の現状の位置付け2019
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杉本真也, 長沼誠, 福田知広, 南木康作, 水野慎大, 木村佳代子, 高林馨, 井上詠, 緒方晴彦, 岩男泰, 金井隆典
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[Presentation] 広範な潰瘍性病変を呈したアメーバ性大腸炎の一例.2019
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