Role of enteric neurons in regulation of intestinal inflammation

• Project/Area Number: 25460942
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Chiba University
• Principal Investigator: fujimura lisa 千葉大学, バイオメディカル研究センター, 助教 (30376363)
• Co-Investigator(Kenkyū-buntansha): HATANO Masahiko 千葉大学, 大学院医学研究院, 教授 (20208523)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腸管神経 / 腸炎 / 腸内細菌叢 / 腸内細菌科 / DSS誘導腸炎モデル / dysbiosis / 好酸球 / 一酸化窒素 / ニトロ化 / NO還元酵素 / 腸内フローラ / 腸内細菌化 / nNOS / ＩｇＡ

Outline of Final Research Achievements

Ncx-deficient (KO) mice exhibited increased number of enteric neuron (EN) and hyper sensitive to DSS induced colitis model. In this study, we characterized the fecal microbiota to examine whether increased number of EN affects enteric flora. CFUs of aerobic bacteria increased in the KO mice compared to those of wild type mice. Meta-genome analysis revealed that the family Enterobacteriaceae were significantly higher in the KO mice compared with the wild type mice. Since bacterial NO reductase gene V (NorV) which detoxificate NO, determine a virulence of bacteria, more NorV+ bacteria were detected from the feces of the KO mice compared to that of wild type mice. To elucidate whether the dysbiosis affect the severity of the DSS-induced colitis, fecal transfer experiments were carried out. Mice transferred with feces of the KO mice developed more severe colitis than wild type transferred one. Our study implies that EN participates in regulation of intestinal microbiota.

Research Products

• [Journal Article] Nepro is localized in the nucleolus and essential for preimplantation development in mice. (2015)
  • Author(s): Masakazu Hashimoto, Tatsuya Sato, Yuko Muroyama, Lisa Fujimura, Masahiko Hatano, Tetsuichiro Saito
  • Journal Title: Development, Growth & Differentiation Volume: 57 Issue: 7 Pages: 529-538
  • DOI: 10.1111/dgd.12232
  • Peer Reviewed
• [Journal Article] Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells. (2014)
  • Author(s): Ikari J, Inamine A, Yamamoto T, Watanabe-Takano H, Yoshid a N, Fujimura L, Taniguchi T, Sakamoto A, Hatano M, Tatsumi K, Tokuhisa T, Arima M.
  • Journal Title: Allergy. Volume: 69 Issue: 2 Pages: 223-230
  • DOI: 10.1111/all.12328
  • Peer Reviewed / Open Access
• [Journal Article] Integration of the mouse sperm fertilization-related protein equatorin into the acrosome during spermatogenesis as revealed by super-resolution and immunoelectron microscopy (2013)
  • Author(s): Ito C, Yamatoya K, Yoshida K, Fujimura L, Hatano M, Miyado K, Toshimori K
  • Journal Title: Cell Tissue Res Volume: 352(3) Issue: 3 Pages: 739-750
  • DOI: 10.1007/s00441-013-1605-y
  • Peer Reviewed
• [Journal Article] Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis. (2013)
  • Author(s): Takahashi W, Watanabe E, Fujimura L, Watanabe-Takano H, Yoshidome H, Swanson PE, Tokuhisa T, Oda S, Hatano M.
  • Journal Title: Crit Care. Volume: １７
  • Peer Reviewed
• [Journal Article] Tumor-suppressive microRNA-29a inhibits cancer cell migration and invasion via targeting HSP47 in cervical squamous cell carcinoma. (2013)
  • Author(s): Yamamoto N, Kinoshita T, Nohata N, Yoshino H, Itesako T, Fujimura L, Mitsuhashi A, Usui H, Enokida H, Nakagawa M, Shozu M, and Seki N
  • Journal Title: Int J Oncol Volume: 43 Issue: 6 Pages: 1855-1863
  • DOI: 10.3892/ijo.2013.2145
  • Peer Reviewed
• [Presentation] Role of enteric neurons in regulation of intestinal homeostasis (2015)
  • Author(s): Lisa Fujimura, Akemi Sakamoto, Masafumi Arima, Takeshi Tokuhisa, Masahiko Hatano
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 北海道札幌市(札幌コンベンションセンター）
  • Year and Date: 2015-11-18
• [Presentation] 腸管恒常性維持における腸管神経の役割について (2015)
  • Author(s): 藤村理紗, 小原由紀子, 大崎敬子, 神谷茂, 幡野雅彦
  • Organizer: 第19回腸内細菌学会
  • Place of Presentation: 東京都港区（北里大学コンベンションホール）
  • Year and Date: 2015-06-18
• [Presentation] Role of enteric neurons in regulation of intestinal epithelial homeostasis (2014)
  • Author(s): Lisa Fujimura, Yukiko Ohara, Akemi Sakamoto, Masafumi Arima, Takeshi Tokuhisa, Masahiko Hatano
  • Organizer: 第43回日本免疫学会
  • Place of Presentation: 国立京都国際会館(京都府京都市)
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Possible role of enteric neurons in regulation of intestinal mucosa. (2013)
  • Author(s): Lisa Fujimura, Yukiko Ohara, Masafumi Arima, Akemi Sakamoto, takeshi Tokuhisa, Masahiko Hatano
  • Organizer: 第42回日本免疫学会
  • Place of Presentation: 千葉(幕張メッセ）
• [Remarks] 千葉大学バイオメディカル研究センター
  • URL: http://www.m.chiba-u.ac.jp/class/biomedical/