The regulation of Paneth cells gene expression by Hath1

• Project/Area Number: 21790653
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TSUCHIYA Kiichirou Tokyo Medical and Dental University, 医学部附属病院, 講師 (40376786)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Atoh1 / Hath1 / 小腸 / パネート細胞 / 抗菌物質 / FGFシグナル / TCF4 / HD6 / クローン病 / 小腸上皮細胞 / 炎症性腸疾患

Research Abstract

Previous studies have indicated that Hath1 contributes to the differentiation program of Paneth cells, however it remains unknown how Hath1 regulates the Paneth cell gene expression. This study shows the mechanism of phenotypic expression for Paneth cells by Hath1 in human intestine. The present study suggests that Hath1 and beta-catenin are essential for HD6 gene expression by binding to E-box sequence in 5' promoter region of HD6 resulting in the contribution to Paneth cell phenotype.

Research Products

• [Journal Article] The suppression of Hath1 gene expression directly regulated by Hes1 via Notch signaling is associated with goblet cell depletion in ulcerative colitis. (2011)
  • Author(s): Zheng X, Tsuchiya K, Okamoto R, Iwasaki M, Kano Y, Sakamoto N, Nakamura T, Watanabe M
  • Journal Title: Inflamm Bowel Dis. in press
  • Peer Reviewed
• [Journal Article] Upregulated IL-7 Receptor {alpha} Expression on Colitogenic Memory CD4+ T Cells May Participate in the Development and Persistence of Chronic Colitis. (2011)
  • Author(s): Shinohara T, Nemoto Y, Kanai T, Kameyama K, Okamoto R, Tsuchiya K, Nakamura T, Totsuka T, Ikuta K, Watanabe M
  • Journal Title: J Immunol. in press
  • Peer Reviewed
• [Journal Article] The suppression of Hath1 gene expression directly regulated by Hes1 via Notch signaling is associated with goblet cell depletion in ulcerative colitis. (2011)
  • Author(s): Zheng X, Tsuchiya K, Watanabe M, et al.
  • Journal Title: Inflamm Bowel Dis. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Magnetic resonance enterocolonography is useful for simultaneous evaluation of small and large intestinal lesions in Crohn's disease. (2010)
  • Author(s): Hyun SB, Kitazume Y, Nagahori M, Toriihara A, Fujii T, Tsuchiya K, Suzuki S, Okada E, Araki A, Naganuma M, Watanabe M.
  • Journal Title: Inflamm Bowel Dis. in press
  • Peer Reviewed
• [Journal Article] Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4. (2010)
  • Author(s): Iwasaki M, Tsuchiya K, Okamoto R, Zheng X, Kano Y, Okamoto E, Okada E, Araki A, Suzuki S, Sakamoto N, Kitagaki K, Akashi T, Eishi Y, Nakamura T, Watanabe M
  • Journal Title: J Gastroenterol in press
  • NAID: 10029027237
  • Peer Reviewed
• [Journal Article] Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells. (2010)
  • Author(s): Nishimura-Sakurai Y, Tsuchiya K, Watanabe M(他18名、18番目)
  • Journal Title: J Gastroenterol. 45 Pages: 523-536
  • NAID: 10027216127
  • Peer Reviewed
• [Journal Article] Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells. (2010)
  • Author(s): Akiyama J, Tsuchiya K, Watanabe M(他5名、6番目)
  • Journal Title: Biochemical and Biophysical Research Communications. 393 Pages: 662-667
  • Peer Reviewed
• [Journal Article] Inhibition of HCV replication by a specific inhibitor of serin-arginine-rich protein kinase. (2010)
  • Author(s): Karakama Y, Tsuchiya K, Watanabe M(他10名、10番目)
  • Journal Title: Antimicrob Agent Chemother. 54(8) Pages: 3179-3186
  • Peer Reviewed
• [Journal Article] Cell culture and in-vivo analyses of plaque-derived cytopathic hepatitis C virus mutants. (2010)
  • Author(s): Mishima K, Tsuchiya K, Watanabe M(他12名、10番目)
  • Journal Title: Virology. 405(2) Pages: 361-369
  • Peer Reviewed
• [Journal Article] IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones. (2010)
  • Author(s): Suda G, Tsuchiya K, Watanabe M(他15名、14番目)
  • Journal Title: Virology. 407(1) Pages: 80-90
• [Journal Article] IL-2 is positively involved in the development of colitogenic CD4+ IL-7R alpha high memory T cells in chronic colitis. (2010)
  • Author(s): Kameyama K, Tsuchiya K, Watanabe M(他8名、6番目)
  • Journal Title: Eur J Immunol 40(9) Pages: 2423-2436
  • Peer Reviewed
• [Journal Article] Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4. (2010)
  • Author(s): Iwasaki M, Tsuchiya K, Watanabe M, et al.
  • Journal Title: J Gastroenterol. Volume: (in press)
  • NAID: 10029027237
  • Peer Reviewed
• [Journal Article] Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells. (2010)
  • Author(s): Akiyama J, Tsuchiya K, Watanabe M, et al.
  • Journal Title: Biochemical and Biophysical Research Communications. Volume: 393 Pages: 662-667
  • Peer Reviewed
• [Journal Article] Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells (2010)
  • Author(s): Akiyama J, Tsuchiya K, et al.
  • Journal Title: Biochemical and Biophysical Research Communications (in press)
  • Peer Reviewed
• [Journal Article] Long-Lived Colitogenic CD4+ Memory T Cells Residing Outside the Intestine Participate in the Perpetuation of Chronic Colitis. (2009)
  • Author(s): Nemoto Y, Tsuchiya K, Watanabe M(他9名、8番目)
  • Journal Title: J Immunol 183 Pages: 5059-5068
  • Peer Reviewed
• [Journal Article] RANK-RANKL Signaling Pathway Is Critically Involved in the Function of CD4+CD25+ Regulatory T Cells in Chronic Colitis. (2009)
  • Author(s): Totsuka T, Tsuchiya K, Watanabe M(他9名、6番目)
  • Journal Title: J Immunol. 182 Pages: 6079-6087
  • Peer Reviewed
• [Journal Article] Signaling pathway via TNF α/NFκB in intestinal epithelial cells may bedirectly involved in colitis- associated carcinogenesis. (2009)
  • Author(s): Onizawa M, Tsuchiya K, Watanabe M(他13名、12番目)
  • Journal Title: Am J Physiol GI & Liver. 296
  • Peer Reviewed
• [Journal Article] Requirement of Notch activation during regeneration of the intestinal epithelia. (2009)
  • Author(s): Okamoto R, Tsuchiya K, Watanabe M(他4名、2番目)
  • Journal Title: Am J Physiol GI & Liver. 296
  • Peer Reviewed
• [Journal Article] Musashi-1 suppresses expression of Paneth cell specific genes in human intestinal epithelial cells. (2009)
  • Author(s): Murayama M, Tsuchiya K, Watanabe M(他6名、3番目)
  • Journal Title: J Gastroenterol. 44 Pages: 173-182
  • NAID: 10025173646
  • Peer Reviewed
• [Journal Article] Single-operator double-balloon endoscopy (DBE) is as effective as dual-operator DBE. (2009)
  • Author(s): Araki A, Tsuchiya K, Watanabe M.(他6名、2番目)
  • Journal Title: J Gastroenterol Hepatol. 24(5) Pages: 770-775
  • Peer Reviewed
• [Journal Article] Signaling pathway via TNFα/NFκB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis (2009)
  • Author(s): Onizawa M, Tsuchiya K, et al.
  • Journal Title: Am J Physiol GI & Liver 296
  • Peer Reviewed
• [Journal Article] Requirement of Notch activation during regeneration of the intestinal epithelia (2009)
  • Author(s): Okamoto R, Tsuchiya K, et al.
  • Journal Title: Am J Physiol GI & Liver 296
  • Peer Reviewed
• [Journal Article] Long-Lived colitogenic CD4+ Memory T Cells residing outside the intestine participate in the perpetuation of chronic colitis (2009)
  • Author(s): Nemoto Y, Tsuchiya K, et al.
  • Journal Title: J Immunol. 183 Pages: 5059-5068
  • Peer Reviewed
• [Journal Article] Musashi-1 suppresses expression of Paneth cell specific genes in human intestinal epithelial cells (2009)
  • Author(s): Murayama M, Tsuchiya K, et al.
  • Journal Title: J Gastroenterol. 44 Pages: 173-182
  • NAID: 10025173646
  • Peer Reviewed
• [Journal Article] RANK-RANKL signaling pathway is critically involved in the function of CD4+CD25+ regulatory T Cells in chronic colitis (2009)
  • Author(s): Totsuka T, Tsuchiya K, et al.
  • Journal Title: J Immunol. 182 Pages: 6079-3087
  • Peer Reviewed
• [Journal Article] IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ memory T cells in chronic colitis (2009)
  • Author(s): Tomita T, Tsuchiya K, et al.
  • Journal Title: Eur J Immunol. 39 Pages: 2737-2747
  • Peer Reviewed
• [Presentation] Silencing of Atoh1 gene expression by Hes1 via Notch signaling results in the goblet cell depletion of Ulcerative Colitis. (2010)
  • Author(s): Tsuchiya K, Okamoto R, Watanabe M
  • Organizer: 14th International Congress of Immunology.
  • Place of Presentation: Kobe.
  • Year and Date: 2010-09-25
• [Presentation] The contribution of Atoh1/Hath1 to phenotypic gene expression for Paneth cells. (2010)
  • Author(s): Tsuchiya K, Okamoto R, Watanabe M
  • Organizer: DDW2010.
  • Place of Presentation: New Orleans.
  • Year and Date: 2010-05-05
• [Presentation] Hes1 via Notch signaling directly suppresses Atoh1/Hath1 gene transcription, resulting in the goblet cell depletion of Ulcerative Colitis. (2010)
  • Author(s): Xiu Zheng, Tsuchiya K, Watanabe M
  • Organizer: DDW2010
  • Place of Presentation: New Orleans.
  • Year and Date: 2010-05-05
• [Presentation] The contribution of Atoh1/Hath1 to phenotypic gene expression for Paneth cells. (2010)
  • Author(s): Tsuchiya K, Okamoto R, Watanabe M
  • Organizer: DDW2010
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-05
• [Presentation] Colon carcinogenesis is divided in the undifferentiation and proliferation regulated by Atoh1 and beta-catenin on Wnt signaling, respectively. (2009)
  • Author(s): Tsuchiya K, Okamoto R, Watanabe M
  • Organizer: UEGW2009.
  • Place of Presentation: London.
  • Year and Date: 2009-11-23
• [Presentation] Colon carcinogenesis is divided in the undifferentiation and proliferation regulated by Atoh1 and beta-catenin on Wnt signaling, respectively (2009)
  • Author(s): Tsuchiya K, et al.
  • Organizer: GASTRO2009
  • Place of Presentation: London
  • Year and Date: 2009-11-23
• [Presentation] GSK3 inhibitor induces the intestinal differentiation by the protein stabilization of Atoh1 (2009)
  • Author(s): Tsuchiya K, et al.
  • Organizer: DDW2009
  • Place of Presentation: Chicago
  • Year and Date: 2009-06-02
• [Remarks] ホームページ
  • URL: http://www.tmd.ac.jp/grad/gast/gast.htm