Analysis of the role of the dietary-derived factor genistein on intestinal epithelium
Project/Area Number |
21K15991
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Kawamoto Ami 東京医科歯科大学, 医学部附属病院光学診療部, 助教 (70849124)
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Project Period (FY) |
2021-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | ゲニステイン / イソフラボン / 潰瘍性大腸炎 / ヒト大腸上皮オルガノイド / チロシンキナーゼ / EGF / HGF / 腸上皮オルガノイド |
Outline of Research at the Start |
炎症性腸疾患(IBD)は消化管における炎症の寛解・増悪と難治性潰瘍の形成を特徴とする難病である。IBDは遺伝的素因・免疫調節機構の破綻・腸内細菌叢の異常の他、食餌等に由来する環境因子等が複合的に関わり発症・成立する。研究代表者の施設も参加し実施された本邦の大規模な患者対照研究では、潰瘍性大腸炎発症に関わる食餌由来因子としてイソフラボン類が同定されている。そこで本研究では腸上皮のイソフラボン応答に関する研究代表者ら独自の知見に基づき「チロシンキナーゼ阻害」から腸上皮増殖能抑制、創傷治癒遅滞に至る分子経路の全貌を明らかにする。更に同応答の成体大腸炎モデルにおける表現型についても解析を試みる。
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Outline of Final Research Achievements |
In this study, functional analysis of the isoflavone genistein in the intestinal epithelium using patient-derived human intestinal epithelial organoids showed that genistein has inhibitory effects on the proliferative function of colonic epithelial stem/progenitor cells by selectively inhibiting both EGF and HGF receptors. Furthermore, genistein significantly delayed the wound healing response in a two-dimensional monolayer epithelial wound healing model using patient-derived colonic epithelial organoids. These results indicate that genistein may negatively affect the intestinal mucosa by suppressing stem/progenitor cell function, leading to persistent mucosal damage and possibly lead to the development of ulcerative colitis.
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Academic Significance and Societal Importance of the Research Achievements |
本邦においてクローン病に対し脂質制限や栄養療法が行われているがその詳細なメカニズムは明らかでない。食餌由来因子と炎症性腸疾患の発症・進展等について特定の食餌因子が腸上皮に対する直接作用を通じて疾患発症に関与し得る機序を示した報告はない。イソフラボン類は本邦で摂取量が多い食餌因子群であり、健康維持に正の効果を有する作用が広く認知されているが、本研究により同因子群のうち、ゲニステインは腸上皮を介した生体に対する負の作用を有し得る当方独自の知見を得た。従って本研究はイソフラボン類の新たな作用機序を明らかとし、今後新たな予防・治療法等への展開に寄与し得るものと考えている。
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Serum Leucine-Rich α2 Glycoprotein: A Novel Biomarker for Transmural Inflammation in Crohn's Disease2022
Author(s)
Kento Takenaka, Yoshio Kitazume, Ami Kawamoto, Toshimitsu Fujii, Yumi Udagawa, Ryosuke Wanatabe, Hiromichi Shimizu, Shuji Hibiya, Masakazu Nagahori, Kazuo Ohtsuka, Hiroyuki Sato, Akihiro Hirakawa, Mamoru Watanabe, Ryuichi Okamoto
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Journal Title
Am J Gastroenterol.
Volume: -
Issue: 6
Pages: 1028-1035
DOI
Related Report
Peer Reviewed
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[Journal Article] Deep neural network for video colonoscopy of ulcerative colitis: a cross-sectional study2022
Author(s)
Kento Takenaka, Toshimitsu Fujii, Ami Kawamoto, Kohei Suzuki, Hiromichi Shimizu, Chiaki Maeyashiki, Osamu Yamaji, Maiko Motobayashi, Akira Igarashi, Ryoichi Hanazawa, Shuji Hibiya, Masakazu Nagahori, Eiko Saito, Ryuichi Okamoto, Kazuo Ohtsuka, Mamoru Watanabe
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Journal Title
Lancet Gastroenterol Hepatol
Volume: 7
Issue: 3
Pages: 230-237
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pancolonic endoscopic and histologic evaluation for relapse prediction in patients with ulcerative colitis in clinical remission2021
Author(s)
Kaneshiro M, Takenaka K, Suzuki K, Fujii T, Hibiya S, Kawamoto A, Motobayashi M, Shimizu H, Nagahori M, Saito E, Okamoto R, Ohtsuka K, Watanabe M.
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Journal Title
Aliment Pharmacol Ther.
Volume: 53(8)
Issue: 8
Pages: 900-907
DOI
Related Report
Peer Reviewed
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[Journal Article] Higher concentrations of cytokine blockers are needed to obtain small bowel mucosal healing during maintenance therapy in Crohn's disease2021
Author(s)
Kento Takenaka, Ami Kawamoto, Shuji Hibiya, Kohei Suzuki, Toshimitsu Fujii, Maiko Motobayashi, Hiromichi Shimizu, Masakazu Nagahori, Eiko Saito, Ryuichi Okamoto, Mamoru Watanabe, Kazuo Ohtsuka
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Journal Title
Aliment Pharmacol Ther
Volume: 54
Issue: 8
Pages: 1052-1060
DOI
Related Report
Peer Reviewed
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[Journal Article] Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus2021
Author(s)
Hiromichi Shimizu, Toshimitsu Fujii, Kenji Kinoshita, Ami Kawamoto, Shuji Hibiya, Kento Takenaka, Eiko Saito, Masakazu Nagahori, Kazuo Ohtsuka, Mamoru Watanabe, Ryuichi Okamoto
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Journal Title
BMC Gastroenterol
Volume: 21
Issue: 1
Pages: 494-494
DOI
Related Report
Peer Reviewed / Open Access
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