TWEAK is involved in DNA damage in intestinal epithelial cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: DOHI Taeko 独立行政法人国立国際医療研究センター, 研究所 肝炎・免疫研究センター 消化器疾患研究部, 部長 (60250221)
• Co-Investigator(Renkei-kenkyūsha): KAWAMURA I Yuki 国立国際医療研究センター研究所肝炎・免疫研究センター, 消化器疾患研究部, 病態生理研究研究室長・室長 (10392391) ; ISHIZAKA Yukihito 国立国際医療研究センター研究所, 副所長 (30281687)
• Research Collaborator: OTSUBO Takeshi 国立国際医療研究センター研究所肝炎・免疫研究センター, 消化器疾患研究部, 特任研究員 (00623034) ; KAWASHIMA Rei 北里大学, 医療衛生学部, 助教 (70392389) ; BURKLY Linda C. Distinguished Investigator, Departments of Immunobiology and Drug Discovery, Biogen Idec
• Project Period (FY): 2011 – 2013
• Keywords: 消化管上皮細胞 / TWEAK / Fn14 / DNA傷害 / 炎症

Research Abstract

TNF-like weak inducer of apoptosis (TWEAK) is a member of TNF superfamily (TNFSF). Its receptor FGF-inducible molecule-14 (Fn14) has been identified. DNA damage is induced by gamma-irradiation and anti-cancer drugs. Gastrointestinal mucosal damage is one of the most significant side-effects of these treatments, which limits the dose of treatment. In this study, we found that TWEAK/Fn14 pathway is significantly involved in the DNA damage of intestinal mucosa that induced by gamma-irradiation and some type of anti-cancer drugs. Particularly, TWEAK enhances death signal mediated by Tumor necrosis factor (TNF)-alfa. results suggest the possible application of TWEAK inhibitors to prevent mucosal damage in cancer therapy.

Research Products

• [Journal Article] Dysbiosis of Salivary Microbiota in Inflammatory Bowel Disease and Its Association With Oral Immunological Biomarkers (2014)
  • Author(s): Said HS, Suda W, Nakagome S, Chinen H, Oshima K. Kim S. Kimura R, Iraha A, Ishida H, Fujita J, Mano S, Morita H, Dohi T, Oota H, Hattori M
  • Journal Title: DNA Research Volume: 21 Pages: 15-25
  • DOI: 10.1093/dnares/dst037
• [Journal Article] Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice (2014)
  • Author(s): Inagaki-Ohara K, Mayuzumi H, Kato S, Minokoshi Y, Otsubo T, Kawamura YI, Dohi T, Matsuzaki G, Yoshimura A
  • Journal Title: Oncogene Volume: 33 Pages: 74-84
  • DOI: 10.1038/onc.2012.540
• [Journal Article] Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1 (2013)
  • Author(s): Iijima K. Okudaira N, Tamura M, Doi A, Saito Y, Shimura M, Goto M, Matsunaga A, Kawamura YI, Otsubo T, Dohi T, Hoshino S, Kano S, Hagiwara S, Tanuma J, Gatanaga H, Baba M, Iguchi T, Yanagita M, Oka S, Okamura T, Ishizaka Y
  • Journal Title: Retrovirology Volume: 10 Pages: 83
  • DOI: 10.1186/1742-4690-10-83
• [Journal Article] TWEAK/Fn14 pathway promotes a T helper 2-type chronic colitis with fibrosis in mice (2013)
  • Author(s): Son A, Oshio T, Kawamura YI, Hagiwara T, Yamazaki M, Inagaki-Ohara K, Okada T, Wu P, Iseki M, Takaki S, Burkly LC, Dohi T
  • Journal Title: Mucosal Immunology Volume: 6 Pages: 1131-1142
  • DOI: 10.1038/mi.2013.10
• [Journal Article] Oral treatment with a novel small molecule alpha 4 integrin antagonist, AJM300, prevents the development of experimental colitis in mice (2013)
  • Author(s): Sugiura T, Kageyama S, Andou A, Miyazawa T, Ejima C, Nakayama A, Dohi T, Eda H
  • Journal Title: J Crohns Colitis Volume: 7 Pages: e533-42
  • DOI: 10.1016/j.crohns.2013.03.014
• [Journal Article] Microbiota derived lactate accelerates colon epithelial cell turnover in starvation-refed mice (2013)
  • Author(s): Okada T, Fukuda S, Hase K, Nishiumi S, Izumi Y, Yoshida M, Hagiwara T, Kawashima R, Yamazaki M, Oshio T, Otsubo T, Inagaki-Ohara K, Kakimoto K, Higuchi K, Kawamura YI, Ohno H, Dohi. T
  • Journal Title: Nature Communications Volume: 4 Pages: 1654
  • DOI: 10.1038/ncomms2668
• [Journal Article] IBD 実験腸炎の病理を知る (2013)
  • Author(s): 土肥多惠子
  • Journal Title: IBD research Volume: 7(3) Pages: 176-181
  • URL: http://www.koyodo.com/goods_detail.cgi?hwsbid=90196&msb=1
• [Journal Article] マイクロバイオームと絶食-再摂食における消化管上皮細胞応答/ マイクロバイオームと疾患 (2013)
  • Author(s): 岡田俊彦、土肥多惠子
  • Journal Title: 医学のあゆみ Volume: 246(3) Pages: 1084-1088
  • URL: http://www.ishiyaku.co.jp/magazines/ayumi/AyumiArticleDetail.aspx?BC=924613&AC=13168
• [Journal Article] 炎症性腸疾患に関連した動物実験モデル (2012)
  • Author(s): 土肥 多惠子
  • Journal Title: 日本臨床 増刊号炎症性腸疾患 Volume: 70 Pages: 122-127
  • URL: http://www.nippon-rinsho.co.jp/backnum/z_mokuji/7002ensho.htm
• [Journal Article] Comprehensive analysis of chemokines and cytokines secreted in the peritoneal cavity during laparotomy (2012)
  • Author(s): Kawashima R, Kawamura YI, Oshio T, Mizutani N, Okada T, Kawamura YJ, Konishi F, Dohi T
  • Journal Title: J Immunoassay Immunochem 2011 Volume: 141 Pages: 2119-2129
  • DOI: 10.1080/15321819.2011.638409
• [Journal Article] Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors siglec-7 and-9 (2012)
  • Author(s): Miyazaki K, Sakuma K, Kawamura YI, Izawa M, Ohmori K, Mitsuki M, Yamaji T, Hashimoto Y, Suzuki A, Saito Y, Dohi T, Kannagi R
  • Journal Title: J Immunol Volume: 188 Pages: 4690-700
  • DOI: 10.4049/jimmunol.1100605
• [Journal Article] The TWEAK/Fn14 pathway as an aggravating and perpetuating factor in inflammatory diseases; focus on inflammatory bowel diseases (2012)
  • Author(s): Dohi T, Burkly LC
  • Journal Title: J Leukoc Biol Volume: 92 Pages: 265-279
  • DOI: 10.1189/jlb.0112042
• [Journal Article] The TWEAK/Fn14 Pathway in Tissue Remodeling: For Better or for Worse (2011)
  • Author(s): Burkly LC, Dohi T
  • Journal Title: Adv Exp Med Biol Volume: 691 Pages: 305-322
  • DOI: 10.1007/978-1-4419-6612-4_32
• [Journal Article] Interleukin-13 Damages Intestinal Mucosa via TWEAK and Fn14 in Mice - a Pathway Associated with Ulcerative Colitis (2011)
  • Author(s): Kawashima R, Kawamura YI, Oshio T, Son A, Yamazaki M, Hagiwara T, Okada T, Inagaki-Ohara K, Wu P, Szak S, Kawamura YJ, Konishi F, Miyake O, Yano H, Saito Y, Burkly LC, Dohi T
  • Journal Title: Gastroenterology Volume: 141 Pages: 2119-2129
  • DOI: 10.1053/j.gastro.2011.08.040
• [Presentation] TWEAK/Fn14 pathway promotes chronic colitis and fibrosis mediated by IL-13-TSLP axis (2013)
  • Author(s): Dohi T, Kawamura YI, Kawashima R, Son A, Oshio T, Wu P, Burkly LC
  • Organizer: Immunology 2013
  • Place of Presentation: Honolulu
  • Year and Date: 20130503-07
• [Presentation] Cell type-specific, genome-wide epigenetic analysis for lamina propria cells isolated from the colon with ulcerative colitis (2013)
  • Author(s): Otsubo T, Kawamura YI, Dohi T
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2013-12-11
• [Presentation] バレット食道および食道腺癌におけるDNAメチル化異常 (2013)
  • Author(s): 萩原 輝記、秋山 純一、三宅 大、大坪 武史、櫻井俊之、清水利夫、土肥多惠子、河村由紀
  • Organizer: 第86回日本生化学会大会
  • Year and Date: 2013-09-13
• [Presentation] 消化管炎症の重症化・慢性化機構を担う因子 (2013)
  • Author(s): 土肥多惠子
  • Organizer: 第50回日本消化器免疫学会ランチョンセミナー
  • Place of Presentation: 東京
  • Year and Date: 2013-08-01
  • Invited
• [Presentation] Involvement of L1 retrotransposition in murine experimental colitis-cancer model (2013)
  • Author(s): Otusbo T, Kawamura YI, Ishizaka Y, Dohi T
  • Organizer: DDW2013
  • Place of Presentation: Orlando
  • Year and Date: 2013-05-20
• [Presentation] TWEAK/Fn14 pathway mediates IL-13 induced intestinal epithelial cell death (2012)
  • Author(s): Kawashima R, Kawamura YI, Oshio T, Hagiwara T, Okada T, Inagaki–Ohara K, Wu P, Szak S, Kawamura YJ, Konishi F, Miyake O, Yano H, Ichikawa T, Saito Y, Burkly LC And Dohi T
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-05
• [Presentation] TWEAK/Fn14 pathway promotes chronic colitis with Th2-type cytokine responses (2012)
  • Author(s): Dohi T, Son A, Kawamura YI, Inagaki-Ohara K, Oshio T, Burkly LC
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(Oral presentation)
  • Year and Date: 2012-12-05
• [Presentation] The TWEAK/Fn14 pathway as an aggravating and perpuating factor in inflammatory bowel diseases (2012)
  • Author(s): Dohi, T
  • Organizer: The 2nd Kinshukai International Symposium: Inflammatory Bowel Disease: Science, Safety and Clinical Care in IBD
  • Place of Presentation: Osaka
  • Year and Date: 2012-10-27
  • Invited
• [Presentation] 炎症性腸疾患のマウスモデルを用いた病態解析 (2012)
  • Author(s): 土肥多惠子
  • Organizer: 第40回日本臨床免疫学会総会ワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2012-09-28
  • Invited
• [Presentation] IL-13による消化管粘膜傷害におけるTWEAK/Fn14経路の関連性 (2012)
  • Author(s): 川島 麗、土肥多惠子、河村由紀、川上文貴、市川尊文
  • Organizer: 第40回日本潰瘍学会
  • Place of Presentation: 東京
  • Year and Date: 2012-07-14
• [Presentation] IL-13 induces TWEAK-dependent activation of TNF- and intestinal epithelial cell damage –a pathway associated with ulcerative colitis (2012)
  • Author(s): T Dohi, R Kawashima, YI Kawamura, T Oshio, M Yamazaki, T Hagiwara, T Okada, P Wu, S Szak, YJ Kawamura, F Konishi, O Miyake, H Yano, Y Saito, L. C. Burkly
  • Organizer: Digestive Disease Week, 2012
  • Place of Presentation: San Diego, U. S. A(Abstract in; Gastroenterology, Volume 142, Issue 5, Supplement 1, May 2012, PagesS-346-S-347)
  • Year and Date: 2012-05-19
• [Presentation] Interleukin-13 links to TWEAK/Fn14 pathway in intestinal epithelial cell injury (2011)
  • Author(s): Kawashima R, Kawamura YI, Oshio T, Son A, Yamazaki M, Hagiwara T, Okada T, Wu P, Szak S, Kawamura YJ, Konishi F, Miyake O, Yano H, Saito Y, Burkly LC, Dohi T
  • Organizer: TNF 2011
  • Place of Presentation: Awajishima, Hyogo
  • Year and Date: 2011-05-16
• [Remarks]
  • URL: http://www.rincgm.jp/individual/hep02/yan_jiu_nei_rong.html