Epigenetically regulated tissue repair mechanism in gastrointestinal tract

• Project/Area Number: 22590712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: KAWAMURA I. Yuki 独立行政法人国立国際医療研究センター, 肝炎・免疫研究センター・消化器疾患研究部・消化器病態生理研究室, 室長 (10392391)
• Co-Investigator(Renkei-kenkyūsha): TOYOTA Minoru (70270676)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 下部消化管学(小腸、大腸) / 糖鎖 / エピゲノム / 消化管

Research Abstract

In this study, we searched for the factors which promoted the regeneration of damaged gastrointestinal epithelium in the murine colitis model. We found that a group of genes involving in the differentiation to mucin-producing cells and the synthesis of mucins was DNA methylated and their expression were significantly decreased in regenerative epithelial cells isolated from the inflamed colon. Decreased expression of some human homologues was also observed in the ulcerative colitis. In addition, the DNA methylation level of the L-1 retrotransposon was dramatically decreased while the DNA methylation of genes involving in the transcription and the differentiation was accelerated in ulcerative colitis. These results suggest the importance of epigenetic gene regulation for the regeneration of the injured epithelium.

Research Products

• [Journal Article] Colonic epithelial cells express specific ligands for 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(9) Pages: 4690-4700
  • Peer Reviewed
• [Journal Article] The monoclonal antibody HCM31 specifically recognizes the Sd^a tetrasaccharide in goblet cell mucin (2012)
  • Author(s): Tsubokawa D、Goso Y、Kawashima R、Ota H、Nakamura T、Nakamura K、Sato N、Kurihara M、Dohi T、Kawamura YI、Ichikawa T、Ishihara K
  • Journal Title: FEBS Open Bio Volume: 2 Pages: 223-233
  • Peer Reviewed
• [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: Immunoassay Immunochem Volume: 33(3) Pages: 291-301
  • Peer Reviewed
• [Journal Article] Incomplete synthesis of carbohydrate determinants in ulcerative colitis (2012)
  • Author(s): Kawamura YI、Dohi T
  • Journal Title: Nihon Rinsho Volume: 70(1) Pages: 646-650
  • NAID: 40019203412
• [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, Y. I., Izawa, M., Ohmori, K., Mitsuki, M., Yamaji, T., Hashimoto, Y., Suzuki, A., Saito, Y., Dohi, T., and Kannagi, R.
  • Journal Title: J. Immunol Volume: 188 Issue: 9 Pages: 4690-4700
  • DOI: 10.4049/jimmunol.1100605
  • Peer Reviewed
• [Journal Article] The monoclonal antibody HCM31 specifically recognizes the Sda tetrasaccharide in goblet cell mucin (2012)
  • Author(s): Tsubokawa D, Goso Y, Kawashima R, Ota H, Nakamura T, Nakamura K, Sato N, Kurihara M, Dohi T, Kawamura YI, Ichikawa T, Ishihara K
  • Journal Title: FEBS Open Bio Volume: 2 Issue: 1 Pages: 223-233
  • DOI: 10.1016/j.fob.2012.07.006
  • Peer Reviewed
• [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 Volume: 33 Issue: 3 Pages: 291-301
  • DOI: 10.1080/15321819.2011.638409
  • Peer Reviewed
• [Journal Article] Incomplete synthesis of carbohydrate determnants in ulcerative colitis (2012)
  • Author(s): Kawamura YI, Dohi T
  • Journal Title: Nihon Rinsho Volume: 70 Pages: 646-650
• [Journal Article] 潰瘍性大腸炎と糖鎖不全現象炎症性腸疾患-病因解明と診断・治療の最新知見-XII.特論 (2012)
  • Author(s): 河村由紀、土肥多恵子
  • Journal Title: 日本臨床 Volume: 70 Pages: 646-650
• [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、Eu P、Szak S、Kawamura YJ、Konishi F、Miyake O、Yano H、Saito Y、Burkly LC、Dohi T
  • Journal Title: Gastroenterology Volume: 141(6) Pages: 2119-2129
  • Peer Reviewed
• [Journal Article] The epithelia-specific membrane trafficking factor AP-1B secures gut immune homeostasis in mice (2011)
  • Author(s): Takahashi D、Hase K、Kimura S、Nakatsu F、Ohmae M、Mandai Y、Sato T、Date Y、Ebisawa M、Kato T、Obata Y、Kawamura YI、Dohi T、Katsuno T、Yokosuka O、Waguri S、Ohno H
  • Journal Title: Gastroenterology Volume: 141(2) Pages: 621-632
  • Peer Reviewed
• [Journal Article] Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-A pathway associated with ulcerative colitis (2011)
  • Author(s): Kawashina R, Kawamura YI, Oshio T, Son A, Yamazaki M, Hagiwara T, Okada T, Inagaki-Ohara K, Eu 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
  • Peer Reviewed
• [Journal Article] The epithelia-specific membrane trafficking factor AP-1B secures gut immune homeostasis in mice (2011)
  • Author(s): Takahashi D, Hase K, Kimura S, Nakatsu F, Ohmae M, Mandai Y, Sato T, Date Y, Ebisawa M, Kato T, Obata Y, Kawamura YI, Dohi T, Katsuno T, Yokosuka O, Waguri S, Ohno H
  • Journal Title: Gastroenterology Volume: 141 Pages: 621-632
  • Peer Reviewed
• [Journal Article] 炎症-発癌と糖鎖不全現象 (2010)
  • Author(s): 河村由紀
  • Journal Title: 大腸癌フロンティア Volume: 3(3) Pages: 214-218
• [Presentation] Genome-wide epigenomic analysis of lamina propria mononuclear cells isolated from patients with inflammatory bowel disease (2012)
  • Author(s): Kawamura YI、Otsubo T、Oshima K、Endo TA、Toyoda T、Hagiwara T、Kawamura YJ、Konishi F、Yano H、Saito Y、Hattori M、Dohi T
  • Organizer: 日米消化器病学会議
  • Place of Presentation: 東京
• [Presentation] DNA hypermethylation of the Sd^a carbohydrate synthase gene as a possible biomarker for the prognosis of ulcerative colitis (2012)
  • Author(s): Sakurai T、Kawamura YI、Hagiwara T、Otsubo T、Hirano Maeyashiki C、Kojima Y、Gotoda T、Yano H、Saito Y、Kawamura YJ、Konishi F、Dohi T
  • Organizer: 米国消化器病週間
  • Place of Presentation: サンディエゴ
• [Presentation] Genome-wide epigenomic analysis of lamina propria mononuclear cells of inflammatory bowel disease (2012)
  • Author(s): TA、Toyoda T、Hagiwara T、Kawamura YJ、Konishi F、Yano H、Saito Y、Hattori M、Dohi T
  • Organizer: 米国消化器病週間
  • Place of Presentation: サンディエゴ
• [Presentation] Epigenomic analysis for small cell numbers of lamina propria T cells and macrophage/dendritic cell fraction in ulcerative colitis (2012)
  • Author(s): 大坪武史、遠藤高帆、豊田哲郎、大島健志朗、萩原輝記、河村裕、小西文雄、矢野秀朗、斉藤幸夫、服部正平、稲垣匡子、河村由紀、土肥多惠子
  • Organizer: 日本生化学会
  • Place of Presentation: 福岡
• [Presentation] 消化管で見られる癌性糖鎖不全とエピゲノム異常.ワークショップ2癌のepigeneticsとmicroRNA (2011)
  • Author(s): 河村由紀
  • Organizer: 日本病態治療研究会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2011-06-17
• [Presentation] I.L-6, a Potent Inducer of DNA Hypermethylation and Malignant-Type Glycosylation in Ulcerative Colitis (2011)
  • Author(s): 河村由紀
  • Organizer: 米国消化器病週間学会
  • Place of Presentation: ニューオリンズ(米国)
  • Year and Date: 2011-05-03
• [Presentation] IL-6, a potential inducer of DNA hypermethylation and malignant-type glycosylation in ulcerative colitis (2011)
  • Author(s): Kawamura YI、Toyota M、Hagiwara T、Suzuki H、Yamazaki M、Okada T、Kawamura YJ、Konishi F、Yano H、Saito Y、Dohi T
  • Organizer: 米国消化器病週間
  • Place of Presentation: シカゴ
• [Presentation] Establishment of a long term culture of self-replicating colon epithelial cells derived from a mouse model of inflammation-related tumor (2011)
  • Author(s): amazaki M、Kawamura YI、Okada T、Dohi T
  • Organizer: 米国消化器病週間
  • Place of Presentation: シカゴ
• [Presentation] 消化管でみられる癌性糖鎖不全とエピゲノム異常 ワークショップ2 癌のepigeneticsとmicroRNA (2011)
  • Author(s): 河村由紀、豊田実、橋本真一、萩原輝記、山崎元美、河村裕、小西文雄、斉藤幸夫、服部正平、土肥多惠子
  • Organizer: 日本病態治療研究会
  • Place of Presentation: 東京
• [Presentation] パレット食道癌における粘液形質異常 (2010)
  • Author(s): 河村由紀
  • Organizer: 第52回日本消化器病学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-15
• [Presentation] IL-6はDNAメチル基転移酵素の異所性発現を介して潰瘍性大腸炎における糖鎖発現異常を誘導する (2010)
  • Author(s): 河村由紀
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] IL-6 induces expression of DNA methyltransferases, gene silencing, and malignant-type glycosylation in ulcerative colitis and colitic cancer. (2010)
  • Author(s): 河村由紀
  • Organizer: 米国消化器病週間学会
  • Place of Presentation: ニューオリンズ(米国)
  • Year and Date: 2010-05-03
• [Presentation] IL-6 induces expression of DNA methyltransferases, gene silencing, and malignant-type glycosylation in ulcerative colitis and colitic cancer (2010)
  • Author(s): Kawamura YI、Toyota M、Kawashima R、Okada T、Hagiwara T、Kawamura YJ、Konishi F、Matsumoto T、Dohi T
  • Organizer: 米国消化器病週間
  • Place of Presentation: ニューオリンズ
• [Presentation] IL-6誘導性DNA高メチル化がもたらす潰瘍性大腸炎およびcolitic cancerの糖鎖異常 (2010)
  • Author(s): 河村由紀、豊田実、川島麗、萩原輝記、河村裕、小西文雄、斉藤幸夫、松本誉之、神奈木玲児、今井浩三、土肥多惠子
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸
• [Presentation] バレット食道癌における粘液形質異常 ワークショップ22 Barrett食道のサーベイランス・治療を巡って (2010)
  • Author(s): 河村由紀、秋山純一、土肥多惠子
  • Organizer: 日本消化器病学会
  • Place of Presentation: 横浜
• [Presentation] IL-6はDNAメチル基転移酵素の異所性発現を介して潰瘍性大腸炎における糖鎖異常を誘導する (2010)
  • Author(s): 河村由紀、豊田実、Vongsavanh Phongsisay、岡田俊彦、山崎元美、河村裕、小西文雄、斉藤幸夫、鈴木拓、神奈木玲児、松本誉之、今井浩三、土肥多惠子
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪
• [Presentation] Genome-wide epigenomic analysis of lamina propria mononuclear cells isolated from patients with inflammatory bowel disease
  • Author(s): Kawamura YI, Otsubo T, Oshima K, Endo TA, Toyoda T, Hagiwara T, Kawamura YJ, Konishi F, Yano H, Saito Y, Hattori M, Dohi T
  • Organizer: The 6th Japan & US Collaboration Conference in Gastroenterology
  • Place of Presentation: Tokyo, Japan
• [Presentation] DNA hypermethylation of the Sda carbohydrate synthase gene as a possible biomarker for the prognosis of ulcerative colitis
  • Author(s): Sakurai T, Kawamura YI, Hagiwara T, Otsubo T, Hirano Maeyasiki C, Kojima Y, Gotoda T, Yano H, Saito Y, Kawamura YJ, Konishi F, Dohi T
  • Organizer: Digestive Disease Week Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] IL-13 induces TWEAK-dependent activation of TNF-α and intestinal epithelial cell damage –a pathway associated with ulcerative colitis
  • Author(s): Dohi T, Kawashima R, Kawamura YI, Oshio T, Yamazaki M, Hagiwara T, Okada T, Wu P, Szak A, Kawamura YJ, Konishi F, Miyake O, Yano H, Saito Y, Burkly LC
  • Organizer: Digestive Disease Week Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] Genome-wide epigenomic analysis of lamina propria mononuclear cells of inflammatory bowel disease
  • Author(s): Otsubo T, Kawamura YI, Oshima K, Endo TA, Toyoda T, Hagiwara T, Kawamura YJ, Konishi F, Yano H, Saito Y, Hattori M, Dohi T
  • Organizer: Digestive Disease Week Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] 末梢血白血球レクチン発現は炎症性腸疾患の病勢を反映するマーカーである
  • Author(s): 前屋舗 千明、河村 由紀、萩原 輝記、大坪 武史、櫻井 俊之、永田 尚義、小島 康志、秋山 純一、神奈木 玲児、土肥 多恵子
  • Organizer: 第99回 日本消化器病学会総会
  • Place of Presentation: 城山観光ホテル・かごしま県民交流センター（鹿児島県）