Effect of central nervous system on small intestinal cell growth And apoptosis

• Project/Area Number: 20590728
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Saga University
• Principal Investigator: KAZUMA Fujimoto Saga University, 医学部, 教授 (50181392)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 視床下部 / 食欲 / 代謝調節 / 消化吸収 / 小腸粘膜増殖 / 生理作用 / 迷走神経 / メタボリック症候群 / 生活習慣 / 中枢神経 / 小腸 / 粘膜 / 増殖機構 / アポトーシス / 摂食中枢 / 満腹中枢 / アミン類 / 糖類 / レプチン / グレリン / 小腸培養

Research Abstract

The aim of this study is to examine if the hypothalamus, central nervous system, regulates mucosal cell growth and apoptosis in the small intestine. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death.Intestinal mucosal apoptosis decreased by the ventromedial hypothalamus lesions,which induced hyperphagia and obesity. In contrast, sustained anorexia induced by administration of anorectic agents increased intestinal apoptosis. These results indicate that the central nervous system, in addition to local factors, is related to regulation of mucosal homeostasis in the intestinal mucosa.

Research Products

• [Journal Article] Post-allenge hyperglycemia is a significant risk factor for the development of hepatocellular carcinoma in patients with chronic hepatitis C. (2011)
  • Author(s): Takahashi H, Mizuta T, Eguchi Y, Kawaguchi Y, Kuwashiro T, Oeda S, Isoda H, Oza N, Iwane S, Izumi K, Anzai K, Ozaki I, Fujimoto K.
  • Journal Title: J Gastroenterol. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] The pathological role of visceral fat accumulation in steatosis, inflammation, and progression of nonalcoholic fatty liver disease. (2011)
  • Author(s): Eguchi Y, Mizuta T, Sumida Y, Ishibashi E, Kitajima Y, Isoda H, Horie H, Tashiro T, Iwamoto E, Takahashi H, Kwashiorkor T, Soejima S, Kawaguchi Y, Oda Y, Emura S, Iwakiri R, Ozaki I, Euchar T, Ono N, Anza K, Fujimoto K, Koizumi S.
  • Journal Title: J Gastroenterol. 46Suppl.1 Pages: 70-78
  • NAID: 10029030366
  • Peer Reviewed
• [Journal Article] Metabolic factors are associated with serum alanine aminotransferase levels in patients with chronic hepatitis C. (2010)
  • Author(s): Kobayashi Y, Kawaguchi Y, Mizuta T, Kwashiorkor T, Ode S, Ooze N, Takahashi H, Inane S, Euchar Y, Anza K, Ozaki I, Fujimoto K.
  • Journal Title: J Gastroenterol. [Epub ahead of print]
  • NAID: 10029028740
  • Peer Reviewed
• [Journal Article] Regulation of tumor suppressor PDCD4 by novel protein kinase C isoforms. (2010)
  • Author(s): Nakashima M, Hamajima H, Xia J, Iwane S, Kawaguchi Y, Eguchi Y, Mizuta T, Fujimoto K, Ozaki I, Matsuhashi S.
  • Journal Title: Biochem.Biophys.Acta. 1803 Pages: 1020-1027
  • Peer Reviewed
• [Journal Article] Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow. (2010)
  • Author(s): Shiraishi R, Iwakiri R, Fujise T, Kuroki T, Kakimoto T, Takashima T, Sakata Y, Tsunada S, Nakashima Y, Yanagita T, Fujimoto K.
  • Journal Title: J.Gastroenterol. 45 Pages: 625-635
  • NAID: 10027216628
  • Peer Reviewed
• [Journal Article] Age-related fat deposition in multifidus muscle could be a marker for nonalcoholic fatty liver disease. (2010)
  • Author(s): Kitajima Y, Eguchi Y, Ishibashi E, Nakashita S, Aoki S, Toda S, Mizuta T, Ozaki I, Ono N, Eguchi T, Arai K, Iwakiri R, Fujimoto K.
  • Journal Title: J Gastroenterol. 45 Pages: 218-224
  • NAID: 10027214665
  • Peer Reviewed
• [Journal Article] Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow. (2010)
  • Author(s): Shiraishi R, et al
  • Journal Title: J.Gastroenterol. Volume: 45 Pages: 625-635
  • Peer Reviewed
• [Journal Article] Regulation of tumor suppressor PDCD4 by novel protein kinase C isoforms. (2010)
  • Author(s): Nakashima M, et al
  • Journal Title: Biochem.Biophys.Acta. Volume: 1803 Pages: 1020-1027
  • Peer Reviewed
• [Journal Article] Modulation of the transforming growth factor-beta1-induced Smad phosphorylation by the extracellular matrix receptor beta1-integrin. (2009)
  • Author(s): Hamajima H, Ozaki I, Zhang H, Iwane S, Kawaguchi Y, Eguchi Y, Matsuhashi S, Mizuta T, Matsuzaki K, Fujimoto K.
  • Journal Title: Int J Oncol. 35 Pages: 1441-1447
  • Peer Reviewed
• [Journal Article] Down regulation of cyclooxygenase-1 is involved in gastric mucosal apoptosis via death signaling in portal hypertensive rats. (2009)
  • Author(s): Wu B, Zeng L, Lin Y, Wen Z, Chen G, Iwakiri R, Fujimoto K.
  • Journal Title: Cell Res. 19 Pages: 1269-1278
  • Peer Reviewed
• [Journal Article] Inhibition of matrix metalloproteinase expression by menatetrenone, a vitamin K2 analogue. (2009)
  • Author(s): Ide Y, Zhang H, Hamajima H, Kawaguchi Y, Eguchi Y, Mizuta T, Yamamoto K, Fujimoto K, Ozaki I.
  • Journal Title: Oncol Rep. 22 Pages: 599-604
  • Peer Reviewed
• [Journal Article] Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats. (2009)
  • Author(s): Shiraishi R, Fujise T, Kuroki T, Kakimoto T, Miao L, Sakata Y, Tsunada S, Noda T, Iwakiri R, Fujimoto K.
  • Journal Title: J Gastroenterol. 44 Pages: 1026-1035
  • NAID: 10025581768
  • Peer Reviewed
• [Journal Article] Higher arterial stiffness, greater peripheral vascular resistance and lower blood flow in lower-leg arteries are associated with long-term hyperglycaemia in type 2 diabetic patients with normal ankle-brachial index. (2009)
  • Author(s): Suzuki E, Yoshimura T, Omura Y, Sakaguchi M, NishioY, Maegawa H, Hisatomi A, Fujimoto K, Takeda J, Kashiwaki A.
  • Journal Title: Diabetes Metab Res Rev 25 Pages: 363-369
  • Peer Reviewed
• [Journal Article] Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. (2009)
  • Author(s): Ootani A, Li X, Sangiorgi E, Ho OT, Ueno H, Toda S, Sugihara H, Fujimoto K, Weissman IL, Capecchi MR, Kuo CJ.
  • Journal Title: Nature Med 15 Pages: 701-706
  • Peer Reviewed
• [Journal Article] Increased lipid absorption and transport in the small intestine of Zucker obese rats. (2009)
  • Author(s): Anzai K, Fukagawa K, Iwakiri R, Fujimoto K, Akashi K, Tso P.
  • Journal Title: J Clin Biochem Nutr 45 Pages: 82-85
  • NAID: 130004466565
  • Peer Reviewed
• [Journal Article] Hepatitis C virus infection enhances insulin resistance induced by visceral fat accumulation. (2009)
  • Author(s): Eguchi Y, Mizuta T, Ishibashi E, Kitajima Y, Oza N, Nakashita S, Hara M, Iwane S, Takahashi H, Akiyama T, Ario K, Kawaguchi Y, Yasutake T, Iwakiri R, Ozaki I, Hisatomi A, Eguchi T, Ono T, Fujimoto K.
  • Journal Title: Liver Int 29 Pages: 213-220
  • Peer Reviewed
• [Journal Article] Increased lipid absorption and transport in the small intestine of Zucker obese rat (2009)
  • Author(s): Anzai K, et al.
  • Journal Title: J Clin Biochem Nutr 45 Pages: 82-85
  • Peer Reviewed
• [Journal Article] Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. (2009)
  • Author(s): Ootani A, et al.
  • Journal Title: Nature Med 15 Pages: 701-706
  • Peer Reviewed
• [Journal Article] Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats. (2009)
  • Author(s): Shiraishi R, et al.
  • Journal Title: J Gastroenterol. 44 Pages: 1026-1035
  • Peer Reviewed
• [Journal Article] Indigestible material attenuated changes in apoptosis in the fasted rat jejunal mucosa. (2008)
  • Author(s): Kakimoto T, Fujise T, Shiraishi R, Kuroki T, Park JM, Ootani A, Sakata Y, Tsunada S, Iwakiri R, Fujimoto K.
  • Journal Title: Exp Biol Med 233 Pages: 310-316
  • Peer Reviewed
• [Journal Article] Suppression of intestinal mucosal apoptosis by ghrelin in fasted rats. (2008)
  • Author(s): Park JM, Kakimoto T, Kuroki T, Shiraishi R, Fujise T, Iwakiri R, Fujimoto K.
  • Journal Title: Exp Biol Med 233 Pages: 48-56
  • Peer Reviewed
• [Journal Article] Suppression of intestinal mucosal apoptosis by ghrelin in fasted rats (2008)
  • Author(s): Park JM, et al
  • Journal Title: Exp Biol Med 233 Pages: 48-56
  • Peer Reviewed
• [Journal Article] Indigestible material attenuated changes in apoptosis in the fasted rat jejunal mucosa (2008)
  • Author(s): Kakimoto T, et al
  • Journal Title: Exp Biol Med 233 Pages: 310-316
  • Peer Reviewed
• [Journal Article] The interaction between adipose tissue stromal cells and gastric cancer cells : roles of the stromal cells in the progression and HER2-targeted therapy of the cancer.
  • Author(s): Nomoto N, Aoki S, Uchihashi K, Matsunobu A, Koike E, Ootani A, Yonemitsu N, Fujimoto K, Toda S.
  • Journal Title: Cancer Sci in press
  • Peer Reviewed
• [Presentation] 肥満、代謝異常と消化管疾患、病態解明への新たなアプローチ:脂肪組織由来間質細胞はCOX-2非依存性にMARK(pERK-1/2)活性化およびHER2発現抑制を介して、胃癌の進展に関与する (2011)
  • Author(s): 野本菜実絵、戸田修二、藤本一眞
  • Organizer: 第7回日本消化管学会総会学術集会抄録集255(ワークショップ)
  • Place of Presentation: 京都
• [Presentation] Visceral fat accumulation is the first and second hit pathogenesis for development of nonalcoholic fatty liver disease. (2010)
  • Author(s): Eguchi Y, Mizuta T, Kawaguchi Y, Ozaki I, Ono N, Eguchi T, Fujimoto K.
  • Organizer: The Second International Forum of Japanese Society of Gastroenterology.日消誌107:A61(Plenary Oral Presentation)
  • Place of Presentation: Niigata
  • Year and Date: 2010-04-24
• [Presentation] 肝疾患での間質実質相互作用、形質転換から見た治療戦略:細胞接着因子β1-インテグリンによる増殖因子のシグナル伝達への関与の解明 (2010)
  • Author(s): 岩根紳治、尾崎岩太、藤本一眞
  • Organizer: 第52回日本消化器病学会大会日消誌107(Suppl):A79 (ワークショップ)
  • Place of Presentation: 横浜
• [Presentation] 生活習慣病と消化管疾患:生活習慣病と大腸発癌について、ラット発癌モデルでの検討 (2010)
  • Author(s): 冨永直之、白石良介、岩切龍一、藤本一眞
  • Organizer: 第6回日本消化管学会総会学術集会抄録集250(ワークショップ)
  • Place of Presentation: 福岡
• [Presentation] 肝疾患での間質実質相互作用、形質転換から見た治療戦略:細胞接着因子β1-インテグリンによる増殖因子のシグナル伝達への関与の解明 (2010)
  • Author(s): 岩根紳治
  • Organizer: 第52回日本消化器病学会大会ワークショップ
  • Place of Presentation: 横浜
• [Presentation] Long term treatment of dyspepsia and GERD with PPI. (2009)
  • Author(s): 藤本一眞
  • Organizer: 13^<th> International Conference on Gastrointestinal Research.(Split, Croatia) Abstract 33 (Invited Lecture)
  • Year and Date: 2009-09-14
• [Presentation] What regulates appetite, glucose or apo A-IV? (2009)
  • Author(s): 藤本一眞
  • Organizer: Second Karuizawa Seminar.Abstract 5 (Lecture)
  • Place of Presentation: Karuizawa
  • Year and Date: 2009-08-01
• [Presentation] 大腸癌の予防:脂肪長期摂取と大腸発癌ラット発癌モデルでの検討 (2009)
  • Author(s): 白石良介、岩切龍一、藤本一眞
  • Organizer: 第95回日本消化器病学会総会日消誌106:A105(ワークショップ)
  • Place of Presentation: 札幌
• [Presentation] 消化器臓器における幹細胞研究の進歩:In vivo analysis of intestinal stem cells. (2009)
  • Author(s): 大谷顕史、藤本一眞、Kuo K.
  • Organizer: 第95回日本消化器病学会総会日消誌 106:A68(パネルディカスッション)
  • Place of Presentation: 札幌
• [Presentation] 消化器臓器における幹細胞研究の進歩 : In vivo analysis of intestinal stem cells (2009)
  • Author(s): 大谷顕史、藤本一眞、Kuo K.
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
• [Presentation] 消化吸収機能における小腸粘膜の形態維持と中枢神経との関連について (2008)
  • Author(s): 藤瀬剛弘、野田隆博、藤本一眞
  • Organizer: 第39回日本消化吸収学会総会日消誌 105:A628(パネルディカスッション)
  • Place of Presentation: 東京
• [Presentation] Recapitulation of the Wnt-dependent intestinal stem cell niche in long-term culture (2008)
  • Author(s): 大谷顕史、藤本一眞、Calvin Kuo.
  • Organizer: 第94回日本消化器病学会総会日消誌 105: A102(パネルディカスッション)
  • Place of Presentation: 福岡
• [Presentation] 共役リノール酸を用いた大腸発癌抑制効果の検討 (2008)
  • Author(s): 白石良介
  • Organizer: 第50回日本消化器病学会大会
  • Place of Presentation: 東京
• [Book] In : Olives and Olive Oil in Health and Disease Prevention(Azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling and the effects of the olive oil.)(edited by Preedy VR and Watson RR.) (2010)
  • Author(s): Fujise T, Iwakiri R, Shiraishi R, Fujimoto K
  • Publisher: Academic Press.Oxford
• [Book] Azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling and the effects of the olive oil. In : Olives and Olive Oil in Health and Disease Prevention (2010)
  • Author(s): Fujise T, Iwakiri R, Fujimoto K
  • Publisher: Academic press Oxford
• [Remarks] ホームページ等
  • URL: http://www.intmed.med.saga-u.ac.jp/kenkyuugroup/group/gast/kennshuutaisei.htm
• [Remarks] 佐賀大学医学部消化器内科