Role of Reg protein on the maintenance of mucosal homeostasis in the gastrointestinal tract

• Project/Area Number: 26460953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hyogo Medical University
• Principal Investigator: Fukui Hirokazu 兵庫医科大学, 医学部, 准教授 (60378742)
• Co-Investigator(Kenkyū-buntansha): 大島 忠之 兵庫医科大学, 医学部, 准教授 (00381814) ; 渡 二郎 兵庫医科大学, 医学部, 教授 (10311531) ; 三輪 洋人 兵庫医科大学, 医学部, 教授 (80190833)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 遺伝子 / 再生医学 / 臨床 / 感染症 / 免疫学

Outline of Final Research Achievements

Reg protein plays a protective roles against NSAIDs-induced gastrointestinal injury by promoting cell proliferation and anti-apoptosis in the epithelium and endothelium in the gastrointestinal tissues. In addition, Reg protein stimulation increases the expression of tight junction proteins in the epithelial cells by activating Sp1, Akt and ERK signaling, resulting in the enhancement of intercellular barrier function. Gut microbiota plays a pivotal role in the expression of Reg protein, and the induced Reg protein may be involved in the cytokine production and differentiation in immune cells.

Research Products

• [Journal Article] Involvement of gut microbiota in the association between GLP-1/GLP-1 receptor expression and gastrointestinal motility (2017)
  • Author(s): Yang M, Fukui H, Eda H, Xu X, Kitayama Y, Hara K, Kodani M, Tomita T, Oshima T, Watari J, Miwa H
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 312 Issue: 4 Pages: G367-G373
  • DOI: 10.1152/ajpgi.00232.2016
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Involvement of gut microbiota in the association between gastrointestinal motility and 5-HT expression/M2 macrophage behavior in the gastrointestinal tract (2017)
  • Author(s): Yang M, Fukui H, Eda H, Kitayama Y, Hara K, Kodani M, Tomita T, Oshima T, Watari J, Miwa H
  • Journal Title: Mol Med Rep Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effect of Helicobacter pylori infection on the link between GLP-1 expression and motility of the gastrointestinal tract (2017)
  • Author(s): Eda H, Fukui H, Uchiyama R, Kitayama Y, Hara K, Yang M, Kodani M, Tomita T, Oshima T, Watari J, Tsutsui H, Miwa H
  • Journal Title: PLOS One Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of regenerating gene I in claudin expression and barrier function in the small intestine (2016)
  • Author(s): Kitayama Y, Fukui H, Hara K, Eda H, Kodani M, Yang M, Sun C, Yamagishi H, Tomita T, Oshima T, Watari J, Takasawa S, Miwa H.
  • Journal Title: Transl Res Volume: 173 Pages: 92-100
  • DOI: 10.1016/j.trsl.2016.03.007
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Expression of Reg family genes in the gastrointestinal tract of mice treated with indomethacin (2015)
  • Author(s): Sun C, Fukui H, Hara K, Kitayama Y, Eda H, Yang M, Yamagishi H, Tomita T, Oshima T, Watari J, Takasawa S, Chiba T, Miwa H
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 308 Issue: 9 Pages: G736-G744
  • DOI: 10.1152/ajpgi.00362.2014
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] FGF9 from cancer-associated fibroblasts is a possible mediator of invasion and anti-apoptosis of gastric cancer cells (2015)
  • Author(s): Sun C, Fukui H, Hara K, Zhang X, Kitayama Y, Eda H, Tomita T, Oshima T, Kikuchi S, Watari J, Sasako M, Miwa H
  • Journal Title: BMC Cancer Volume: 15 Issue: 1 Pages: 333-333
  • DOI: 10.1186/s12885-015-1353-3
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effect of Effect of REG Ia protein on angiogenesis in gastric cancer tissuesREG I protein on angiogenesis in gastric cancer tissues (2015)
  • Author(s): Hara K, Fukui H, Sun C, Kitayama Y, Eda H, Yamasaki T, Kondo T, Tomita T, Oshima T, Watari J, Fujimori T, Miwa H
  • Journal Title: Oncol Rep Volume: 33 Issue: 5 Pages: 2183-2189
  • DOI: 10.3892/or.2015.3878
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling. (2014)
  • Author(s): Fukui H, Zhang X, Sun C, Hara K, Kikuchi S, Yamasaki T, Kondo T, Tomita T, Oshima T, Watari J, Imura J, Fujimori T, Sasako M, Miwa H
  • Journal Title: Br J Cancer Volume: 111 Issue: 4 Pages: 183-490
  • DOI: 10.1038/bjc.2014.336
  • Peer Reviewed / Open Access
• [Journal Article] Diabetes mellitus increases the risk of early gastric cancer development. (2014)
  • Author(s): Sekikawa A, Fukui H, Maruo T, Tsumura T, Okabe Y, Osaki Y.
  • Journal Title: Eur J Cancer Volume: 50 Issue: 12 Pages: 2065-2071
  • DOI: 10.1016/j.ejca.2014.05.020
  • Peer Reviewed
• [Journal Article] Gastric xanthelasma may be a warning sign for the presence of early gastric cancer. (2014)
  • Author(s): Sekikawa A, Fukui H, Maruo T, Tsumura T, Kanesaka T, Okabe Y, Osaki Y.
  • Journal Title: J Gastroenterol Hepatol Volume: 29 Issue: 5 Pages: 951-956
  • DOI: 10.1111/jgh.12512
  • Peer Reviewed
• [Journal Article] IL-4 induces columnar like differentiation of esophageal squamous epithelium through JAK/PI3K pathway: possible role in pathogenesis of Barrett's esophagus. (2014)
  • Author(s): Shan J, Oshima T, Farre R, Fukui H, Watari J, Miwa H.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 306
  • Peer Reviewed
• [Journal Article] A Randomized, double-blind, placebo-controlled study of rebamipide for gastric mucosal injury taking aspirin with or without clopidogrel. (2014)
  • Author(s): Tozawa K, Oshima T, Okugawa T, Ogawa T, Ohda Y, Tomita T, Hida N, Fukui H, Hori K, Watari J, Nakamura S, Miwa H.
  • Journal Title: Dig Dis Sci Volume: 59 Pages: 1885-1890
  • Peer Reviewed
• [Presentation] Effect of gut microbiota on Reg IIIr expression in relation to intestinal immunity (2017)
  • Author(s): Xin Xu, Fukui H, Eda H, Yamasaki T, Kondo T, Tozawa K, Ohda Y, Tomita T, Oshima T, Watari J, Miwa H
  • Organizer: Biennial Congress of Asian Neurogastroenterology and Motility Association
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2017-03-24
  • Int'l Joint Research
• [Presentation] Role of microbiota in gut hormone and gastrointestinal motility (2017)
  • Author(s): Fukui H
  • Organizer: 2017 Academic Congress of Intestinal Diseases Tianjin&・China
  • Place of Presentation: Tianjin, China
  • Year and Date: 2017-01-08
  • Invited
• [Presentation] Alteration of gastrointestinal motility and mast cell behavior in mice after DSS-induced colitis (2016)
  • Author(s): Kodani M, Fukui H, Tomita T, Oshima T, Watari J, Miwa H.
  • Organizer: Federation of Neurogastroenterology and Motility Meeting 2016
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-08-26
  • Int'l Joint Research
• [Presentation] Effect of REG protein on the link between claudin expression and mucosal permeability in the small intestine (2016)
  • Author(s): Fukui H, Kitayama Y, Hara K, Yamasaki T, Kondo T, Ikehara H, Ohda Y, Tomita T, Oshima T, Watari J, Miwa H
  • Organizer: Annual Meetings of the American Gastroenterology Association and American Association for the Study of Liver Disease at the Digestive Disease Week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-05-24
  • Int'l Joint Research
• [Presentation] Involvement of gut microbiota in the association between macrophage and gastrointestinal motility (2016)
  • Author(s): Yang M, Fukui H, Eda H, Kodani M, Yamasaki T, Kondo T, Ikehara H, Ohda Y, Tomita T, Oshima T, Watari J, Miwa H
  • Organizer: Annual Meetings of the American Gastroenterology Association and American Association for the Study of Liver Disease at the Digestive Disease Week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-05-22
  • Int'l Joint Research
• [Presentation] Effect of H. pylori infection on GLP-1 expression and gastrointestinal motility (2015)
  • Author(s): Eda H, Fukui H, Kitayama Y, Hara K, Yamasaki T, Kondo T, Tozawa K, Ikehara H, Ohda Y, Tomita T, Oshima T, Watari J, Miwa H
  • Organizer: Asia Pacific Digestive Week
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] Effect of REG protein on mucosal permeability and adhesion molecule expression in the small intestine (2015)
  • Author(s): Kitayama Y, Fukui H, Yamasaki T, Kondo T, Kono T, Toyoshima F, Ikehara H, Ohda Y, Tomita T, Oshima T, Watari J, Miwa H
  • Organizer: Annual Meetings of the American Gastroenterology Association and American Association for the Study of Liver Disease at the Digestive Disease Week
  • Place of Presentation: Washington, USA
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Serum Reg Ia is a marker to predict histological and clinical activity in ulcerative colitis (2015)
  • Author(s): Tozawa K, Fukui H, Yamasaki T, Kondo T, Kono T, Toyoshima F, Ikehara H, Ohda Y, Tomita T, Oshima T, Watari J, Miwa H
  • Organizer: Annual Meetings of the American Gastroenterology Association and American Association for the Study of Liver Disease at the Digestive Disease Week
  • Place of Presentation: Washington, USA
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Involvement of STAT3 activation in the development of early gastric cancer (2014)
  • Author(s): Sakamoto H, Fukui H, Kono T, Ikehara H, Tomita T, Oshima T, Watari J, Miwa H
  • Organizer: Asia Pacific Digestive Week
  • Place of Presentation: Bali, Indonesia
  • Year and Date: 2014-11-25
• [Presentation] NSAID 起因性消化管粘膜傷害における Reg 蛋白の役割 (2014)
  • Author(s): 福井広一，原謙，三輪洋人
  • Organizer: 第 56 回日本消化器病学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23
• [Presentation] 胃炎－胃癌相関における STAT3 シグナル活性の意義について (2014)
  • Author(s): 福井広一，渡二郎，三輪洋人
  • Organizer: 第 100 回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24