Novel roles of transporters and adherent molecules of epithelial membrane in the recognition of bacteria

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590931
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Asahikawa Medical College
• Principal Investigator: FUJIYA Mikihiro 旭川医科大学, 医学部, 准教授 (80322915)
• Co-Investigator(Kenkyū-buntansha): OHTAKE Takaaki 旭川医科大学, 医学部, 講師 (10359490)
• Project Period (FY): 2011 – 2013
• Keywords: 下部消化管学（小腸、大腸） / 腸内細菌

Research Abstract

Competence and sporulation factor and polyphosphate were identified as bioactive molecules from the conditioned media of Bacillus subtilis and Lactobacillus brevis SB88, respectively. These molecules improved the intestinal injury through their transport by OCTN2 and binding to integrin 1, respectively. The novel communication systems between the host and bacteria are distinct from the mechanisms mediated by pattern-recognition receptors, such as Toll-like receptors and NODs. These results are therefore expected to positively contribute to the development of new drugs for the treatment of intestinal inflammation using bacteria-derived molecules.

Research Products

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