細胞膜有機イオン輸送体および接着分子による新規微生物認識機構の解明と腸炎への関与

2013 年度 研究成果報告書

• 研究課題/領域番号: 23590931
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 消化器内科学
• 研究機関: 旭川医科大学
• 研究代表者: 藤谷 幹浩 旭川医科大学, 医学部, 准教授 (80322915)
• 研究分担者: 大竹 孝明 旭川医科大学, 医学部, 講師 (10359490)
• 研究期間 (年度): 2011 – 2013
• キーワード: 下部消化管学（小腸、大腸） / 腸内細菌

研究概要

バシラス菌および新規麦芽乳酸菌の培養上清から腸管上皮バリア機能を増強する活性物質であるcompetence and sporulation factor (CSF)とポリリン酸を同定することに成功した。これらの活性物質は、細胞膜トランスポーターOCTN2およびインテグリン1により腸管上皮に認識され、細胞内に取り込まれることで、腸管障害を改善することが明らかになった。これは、Toll様受容体やNODsなどのパターン認識受容体を介さない、新たな宿主－腸内細菌のコミュニケーションシステムの存在を示唆するとともに、菌由来活性物質を用いた新規腸炎治療開発への足がかりとなる。

研究成果

• [雑誌論文] Up-regulation of iron regulatory hormone hepcidin by interferonα (2014)
  • 著者名/発表者名: Ichiki K, Ikuta K, Addo L, Tanaka H, Sasaki Y, Shimonaka Y, Sasaki K, Ito S, Shindo M, Ohtake T, Fujiya M, Torimoto Y, Kohgo Y
  • 雑誌名: J ournal of Gastroenterology and Hepatology 巻: 29(2) ページ: 387-94
• [雑誌論文] Probiotic treatments for induction and maintenance of remission in inflammatory bowel diseases : A meta-analysis of randomized controlled trials (2014)
  • 著者名/発表者名: Fujiya M, et al.
  • 雑誌名: Clin J Gastroenterol 巻: 7(1) ページ: 1-13
• [雑誌論文] Infliximab extends the duration until the first surgery in patients with Crohn's disease (2013)
  • 著者名/発表者名: Sakatani A, Fujiya M, et al.
  • 雑誌名: Biomed Research International 巻: 2013 ページ: 879491
• [雑誌論文] microRNA-146b improves intestinal injury in mouse colitis by activating NF-kB and improving epithelial barrier function (2013)
  • 著者名/発表者名: Nata T, Fujiya M, et al.
  • 雑誌名: J ournal of Gene Medicine 巻: 15(6-7) ページ: 249-60
• [雑誌論文] Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes (2013)
  • 著者名/発表者名: Takahashi N, Yoshizaki T, Hiranaka N, Suzuki T, Yui T, Akanuma M, Kanazawa K, Yoshida M, Naito S, Fujiya M, Kohgo Y, Ieko M
  • 雑誌名: BBRC 巻: 431(1) ページ: 25-30
• [雑誌論文] Image-enhanced endoscopy for the diagnosis of colon neoplasms (2013)
  • 著者名/発表者名: Fujiya M, Kohgo Y
  • 雑誌名: Gastrointest Endosc 巻: 77(1) ページ: 111-118
• [雑誌論文] Competence and sporulation factor derived from Bacillus subtilis improves epithelial cell injury in intestinal inflammation via immunomodulation and cytoprotection (2012)
  • 著者名/発表者名: Okamoto K, Fujiya M, et al.
  • 雑誌名: Int J Colorectal Diseases 巻: 27(8) ページ: 1039-46
• [雑誌論文] Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) versus High Resolution White Light Colonoscopy for Adenoma Detection (2012)
  • 著者名/発表者名: Moriichi K, Fujiya M, et al.
  • 雑誌名: BMC Gastroenterology 巻: 12(1) ページ: 75
• [雑誌論文] Isoleucine, an essential amino acid, induces the expression of human b-defensin 2 through the activation of the G-protein coupled receptor-ERK pathway in the intestinal epithelia (2012)
  • 著者名/発表者名: Konno Y, Ashida T, Inaba Y, Ito T, Tanabe H, Maemoto A, Ayabe T, Mizukami Y, Fujiya M, Kohgo Y
  • 雑誌名: Food and Nutrition Sciences 巻: 3(4) ページ: 548-555
• [雑誌論文] Effect of Lactobacillus brevis SBC8803 on Gamma-Glutamyl Transferase in Japanese Habitual Drinkers : A Double-Blind, Placebo-Controlled Study (2012)
  • 著者名/発表者名: Wakita Y, Shimizu C, Nakakita Y, Kaneda H, Kanda H, Segawa S, Shigyou T, Ohtake T, Fujiya M, Kohgo Y
  • 雑誌名: Food and Nutrition Sciences 巻: 3(5) ページ: 678-684
• [雑誌論文] Iron Uptake Facilitator LS081 Induces The Degradation of Hypoxia Inducible Factor-1 and Functions as Anti-Cancer Agent in Hepatocellular Carcinoma (2012)
  • 著者名/発表者名: Tanaka H, Li Z, Ikuta K, Addo L, Akutsu H, Nakamura M, Sasaki K, Ohtake T, Fujiya M, et al.
  • 雑誌名: Cancer Science 巻: 103(4) ページ: 767-74
• [雑誌論文] Biomarkers predicting development of metachronous after endoscopic resection : an analysis of molecular pathology of Helicobactor pylori eradication (2012)
  • 著者名/発表者名: Watari J, Moriichi K, Tanabe H, Kashima S, Nomura Y, Fujiya M, et al.
  • 雑誌名: Int J Cancer 巻: 130(10) ページ: 2349-58
• [雑誌論文] Autofluorescence imaging and the quantitative intensity of fluorescence for evaluating the dysplastic grade of colonic neoplasms (2012)
  • 著者名/発表者名: Moriichi K, Fujiya M, et al.
  • 雑誌名: Int J Colorectal Diseases 巻: 27 (3) ページ: 325-330
• [雑誌論文] Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes (2011)
  • 著者名/発表者名: Takahashi N, Yoshizaki T, Hiranaka N, Suzuki T, Yui T, Akanuma M, Oka K, Kanazawa K, Yoshida M, Naito S, Fujiya M, Kohgo Y, Ieko M
  • 雑誌名: Biochem Biophys Res Commun 巻: 11;415(1) ページ: 200-5
• [雑誌論文] Heat-killed body of Lactobacillus brevis SBC8803 ameliorates intestinal injury in a murine model of colitis by enhancing the intestinal barrier function (2011)
  • 著者名/発表者名: Ueno N, Fujiya M, et al.
  • 雑誌名: Inflammatory Bowel Diseases 巻: 17(11) ページ: 2235-50
• [雑誌論文] The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma (2011)
  • 著者名/発表者名: Sato R, Fujiya M, et al.
  • 雑誌名: Endoscopy 巻: 43(10) ページ: 862-8
• [雑誌論文] Obscure gastrointestinal bleeding from vascular lesions formed by venous and lymphatic congestion due to post-operative adhesion and subsequent mesenteric torsion 50 years after appendectomy (2011)
  • 著者名/発表者名: Kashima S, Nata T, Fujiya M, et al.
  • 雑誌名: Gut 巻: 60 (10) ページ: 1344
• [雑誌論文] Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway (2011)
  • 著者名/発表者名: Segawa S, Fujiya M, et al.
  • 雑誌名: PloS One 巻: 6 (8) ページ: e23278
• [雑誌論文] Endosopic auto-fluorescence imaging is useful for the differential diagnosis of intestinal lymphomas resembling lymphoid heyperplasia (2011)
  • 著者名/発表者名: Ueno N, Fujiya M, et al.
  • 雑誌名: J Clin Gastroenterol 巻: 45(6) ページ: 507-13
• [雑誌論文] Cytokine Regulation of OCTN2 Expression and Activity in Small and Large Intestine (2011)
  • 著者名/発表者名: Fujiya M, et al.
  • 雑誌名: Inflammatory Bowel Diseases 巻: 17(4) ページ: 907-16
• [雑誌論文] A New Antimesenteric Functional End-to-End Handsewn Anastomosis : Surgical Prevention of Anastomotic Recurrence in Crohn's Disease (2011)
  • 著者名/発表者名: Kono T, Ashida T, Ebisawa Y, Chisato N, Okamoto K, Katsuno H, Maeda K, Fujiya M, Kohgo Y, Furukawa H
  • 雑誌名: Dis Colon Rectum 巻: 54(5) ページ: 586-92
• [雑誌論文] a Japanese traditional medicine, blocks DSS-induced intestinal inflammation and damage
  • 著者名/発表者名: Ueno N, Hasebe T, Kaneko A, Yamamoto M, Wang Y, Fujiya M, Kohgo Y, Kono T, Musch MW, Chang EB. Daikenchuto
  • 雑誌名: PloS One 巻: (in press)
• [雑誌論文] Decreased vessel networks and irregular vessel on narrow band imaging are useful findings to distinguish intestinal lymphoma from lymphoid hyperplasia
  • 著者名/発表者名: Fujiya M, et al.
  • 雑誌名: Gastrointest Endosc 巻: (in press)
• [雑誌論文] microRNA-18a induces apoptosis in colon cancer cells via the autophagolysosomal degradation of oncogenic heterogeneous nuclear ribonucleoprotein A1
  • 著者名/発表者名: Fujiya M, et al.
  • 雑誌名: Oncogene 巻: (in press)
• [雑誌論文] Augmented hepatic Toll-like receptors by fatty acids trigger the pro-inflammatory state of nonalcoholic fatty liver disease in mice
  • 著者名/発表者名: Sawada K, Ohtake T, Hasebe T, Abe M, Tanaka H, Ikuta K, Suzuki Y, Fujiya M, Hasebe C, Kohgo Y
  • 雑誌名: Hepatology Research 巻: (in press)
• [学会発表] Long-term oral dietary administration of a new probiotic, Lactobacillus brevis SBC8803, alters gut the microbiota and ameliorates DSS-induced colitis in mice (2014)
  • 著者名/発表者名: Ueno N, Fujiya M, et al.
  • 学会等名: DDW 2014 (AGA)
  • 発表場所: Chicago
  • 年月日: 2014-05-06
• [学会発表] The novel probiotic function through activation of intestinal epithelial autophagy. The novel probiotic function through activation of intestinal epithelial autophagy (2013)
  • 著者名/発表者名: Inaba Y, Fujiya M, Kohgo Y
  • 学会等名: 16th International Congress of Mucosal Immunology (ICMI 2013)
  • 発表場所: Vancouver
  • 年月日: 2013-07-17
• [学会発表] A probiotic-derived polyphosphate improves chronic inflammation and fibrosis via caveolin-dependent endocytosis (2013)
  • 著者名/発表者名: Fujiya M, et al.
  • 学会等名: GI Research Academy 2013
  • 発表場所: Kyoto
  • 年月日: 2013-06-28
• [学会発表] A probiotic-derived polyphosphate improves chronic inflammation and fibrosis via caveolin-dependent endocytosis (2013)
  • 著者名/発表者名: Konishi H, Fujiya M, et al.
  • 学会等名: DDW 2013 (AGA)
  • 発表場所: Orland
  • 年月日: 2013-05-21
• [学会発表] Probiotic-derived polyphosphate inhibits colon cancer progression through the inactivation of the ERK pathway and the induction of cancer cell apoptosis (2013)
  • 著者名/発表者名: Sakatani A, Fujiya M,et al.
  • 学会等名: DDW 2013 (AGA)
  • 発表場所: Orland
  • 年月日: 2013-05-21
• [学会発表] A polyphosphate derived from Lactobacillus brevis improves the intestinal barrier function and injury in acute and chronic experimental colitis (2013)
  • 著者名/発表者名: Fujiya M, et al.
  • 学会等名: 13th International Conference of FFC
  • 発表場所: Kyoto
  • 年月日: 2013-05-11
• [学会発表] Polyphosphate derived from Lactobacillus contributes to the maintenance of intestinal homeostasis and the improvement of intestinal injury in experimental colitis (2012)
  • 著者名/発表者名: Fujiya M, et al.
  • 学会等名: 10th Asian IBD Symposium
  • 発表場所: Seoul
  • 年月日: 2012-11-03
• [学会発表] Polyphosphate is a novel active molecule derived from Lactobacillus brevis that contributes to the maintenance of intestinal homeostasis and the improvement of intestinal injury in acute and chronic experimental colitis (2012)
  • 著者名/発表者名: Fujiya M, et al.
  • 学会等名: DDW 2012 (AGA)
  • 発表場所: San Diego
  • 年月日: 2012-05-20
• [学会発表] Activation of Intestinal Epithelial Autophagy as a Potential and Novel Mechanism of Probiotic Action in the Gut (2012)
  • 著者名/発表者名: Inaba Y, Fujiya M, Musch MW, Boone D, Kohgo Y, Chang EB
  • 学会等名: 7th Congress of ECCO
  • 発表場所: Barcelona
  • 年月日: 2012-02-16
• [学会発表] Lactobacillus brevis Culture Supernatant Induces Cytoprotective Small Heat Shock Protein HSP27 and Increase Intestinal Barrier Function by Activating the p38 MAPK Pathway (2011)
  • 著者名/発表者名: Segawa S, Fujiya M, et al.
  • 学会等名: 15th International Congress of Mucosal Immunology (ICMI 2011)
  • 発表場所: Paris
  • 年月日: 2011-07-05
• [図書] Trypsin acts as an activating enzyme in gut innate immunity, Trypsin : Structure, Biosynthesis and F unctions Trypsin : Structure, Biosynthesis and Functions, edited by Kirk Weaver and Clayton Kelly (2012)
  • 著者名/発表者名: Tanabe H, Fujiya M, Kohgo Y
  • 総ページ数: 133-139
  • 出版者: Hauppauge (NY): Nova Science Publishers Inc.,(ISBN 978-1-61942-319-0)
• [図書] Autofluorescence imaging for diagnosing intestinal disorders. Colonocopy/Book 1, Edited by Paul Miskovitz (2011)
  • 著者名/発表者名: Fujiya M, Moriichi K, Ueno N, Saitoh Y, Kohgo Y
  • 出版者: InTech, Rijeka (Croatia)
• [産業財産権] 腸管保護剤 (2014)
  • 発明者名: 高後 裕,藤谷幹浩,上野伸展,瀬 川修一,小林直之
  • 権利者名: 旭川医科大学
  • 産業財産権種類: 特許
  • 産業財産権番号: 特許第5526320号
  • 取得年月日: 2014-04-15
  • 外国
• [産業財産権] 消化器癌に対する抗腫瘍剤 (2013)
  • 発明者名: 高後 裕、藤谷幹浩,岡本耕太郎
  • 権利者名: 旭川医科大学
  • 産業財産権種類: 特許
  • 産業財産権番号: 特許第5190849号
  • 取得年月日: 2013-02-08
  • 外国
• [産業財産権] 腸管保護剤 (2011)
  • 発明者名: 高後 裕,藤谷幹浩,上野伸展,瀬 川修一,小林直之
  • 権利者名: 旭川医科大学
  • 産業財産権種類: 特許
  • 産業財産権番号: PCT/JP2011/057689
  • 出願年月日: 2011-03-28
  • 外国