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Searching for the novel biomarker of Hirschsprung disease: focusing on the mechanism of extrinsic nerve fiber development

Research Project

Project/Area Number 15K10929
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionJuntendo University

Principal Investigator

MIYAHARA Katsumi  順天堂大学, 医学(系)研究科(研究院), 研究技師 (00420844)

Co-Investigator(Kenkyū-buntansha) 山高 篤行  順天堂大学, 医学部, 教授 (40200703)
田中 奈々  順天堂大学, 医学部, 准教授 (50530656)
Research Collaborator TAKAHASHI Mirei  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsヒルシュスプルング病 / 腸管神経系 / アセチル化チューブリン / エンドセリンレセプターB / 腸管神経 / 感覚神経 / サブスタンス P / CGRP / 神経堤細胞 / 軸索ガイダンス分子
Outline of Final Research Achievements

Tubulin acetylation is involved in the regulation and stability of microtubule structure and plays an important role in various neuronal functions. In this study, the relationship between the expression of acetylated α-tubulin (Ac-Tub) in enteric neurons of the endothelin receptor B-knockout (EDNRB KO) mouse, which is a mouse model of Hirschsprung disease (HD), and developmental abnormalities of the enteric nervous system (ENS) were examined.
Fluorescent immunohistochemical analysis with Ac-Tub antibody was performed to assess the expression pattern of Ac-Tub in neuronal cells, and the expression in the EDNRB KO embryos was found to be increased compared to that in the normal embryos. The results indicated that the change in Ac-Tub expression in the developing enteric neurons may be associated with developmental abnormalities related to the innervation of the ENS in HD.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2018 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 1 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 14 results,  Invited: 1 results)

  • [Journal Article] Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung's disease.2018

    • Author(s)
      Fujiwara N, Nakazawa-Tanaka N, Miyahara K, Arikawa-Hirasawa E, Akazawa C, Yamataka A
    • Journal Title

      Pediatr Surg Int

      Volume: 34 Issue: 2 Pages: 137-141

    • DOI

      10.1007/s00383-017-4180-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effect of laminin-1 on enteric neural crest-derived cell migration in the Hirschsprung's disease mouse model2018

    • Author(s)
      Nakazawa-Tanaka N, Fujiwara N, Miyahara K, Nakada S, Arikawa-Hirasawa E, Akazawa C, Yamataka A
    • Journal Title

      Pediatr Surg Int

      Volume: 34 Issue: 2 Pages: 143-147

    • DOI

      10.1007/s00383-017-4181-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased expression of Semaphorin 3A in the endothelin receptor-B null mouse model of Hirschsprung disease2018

    • Author(s)
      Fujiwara Naho、Miyahara Katsumi、Nakazawa-Tanaka Nana、Akazawa Chihiro、Yamataka Atsuyuki
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 53 Issue: 2 Pages: 326-329

    • DOI

      10.1016/j.jpedsurg.2017.11.034

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensory innervation of the anal canal and anorectal line in Hirschsprung’s disease: histological evidence from mouse models2017

    • Author(s)
      Takeda Masahiro、Miyahara Katsumi、Akazawa Chihiro、Lane Geoffrey J.、Yamataka Atsuyuki
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 8 Pages: 883-886

    • DOI

      10.1007/s00383-017-4112-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Semaphorin 3A expression following intestinal ischemia/reperfusion injury in Sox10-Venus mice.2017

    • Author(s)
      Takeda M, Miyahara K, Okawada M, Akazawa C, Lane GJ, Yamataka A.
    • Journal Title

      Pediatr Surg Int.

      Volume: 33(3) Issue: 3 Pages: 383-388

    • DOI

      10.1007/s00383-016-4039-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Altered differentiation of enteric neural crest-derived cells from endothelin receptor-B null mouse model of Hirschsprung's disease.2016

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A.
    • Journal Title

      Pediatr Surg Int.

      Volume: 32(12) Pages: 1095-1101

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Three- and four-dimensional analysis of altered behavior of enteric neural crest derived cells in the Hirschsprung's disease mouse model2016

    • Author(s)
      Nakazawa-Tanaka N, Miyahara K, Fujiwara N, Urao M, Akazawa C, Yamataka A
    • Journal Title

      Pediatr Surg Int

      Volume: 32 Issue: 1 Pages: 390-407

    • DOI

      10.1007/s00383-015-3806-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rectal mucosal dissection commencing directly on the anorectal line versus commencing above the dentate line in laparoscopy-assisted transanal pull-through for Hirschsprung's disease: Prospective medium-term follow-up2015

    • Author(s)
      Miyano G, Koga H, Okawada M, Doi T, Sueyoshi R, Nakamura H, Seo S, Ochi T, Yamada S, Imaizumi T, Lane GJ, Okazaki T, Urao M, Yamataka A
    • Journal Title

      J Pediatr Surg

      Volume: 50 Issue: 12 Pages: 2041-2043

    • DOI

      10.1016/j.jpedsurg.2015.08.022

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Altered differentiation of enteric neural crest derived cells from endothelin-B receptor null mouse model of Hirschsprung's disease.2017

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A
    • Organizer
      The 24th International Meeting Colorectal Club
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Laminin promotes neurite growth in the enteric nervous system of the embryonic mouse gut.2017

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A
    • Organizer
      The 18th European Congress of European Paediatric Surgeons' Association
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung's disease.2017

    • Author(s)
      Fujiwara N, Nakazawa-Tanaka N, Miyahara K, Arikawa-Hirasawa E, Akazawa C, Yamataka A
    • Organizer
      The 30th International Symposium on Pediatric Surgical Research and Update on Newborn Surgery
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Increased expression of Semaphorin 3A in the endothelin receptor-B null mouse model of Hirschsprung disease.2017

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A
    • Organizer
      The 64th Annual International Congress of the British Association of Paediatric Surgeons
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effect of laminin-1 on enteric neural crest-derived cell migration in the Hirschsprung's disease mouse model.2017

    • Author(s)
      Nakazawa-Tanaka N, Fujiwara N, Miyahara K, Nakada S, Arikawa-Hirasawa E, Akazawa C, Urao M, Yamataka A
    • Organizer
      The 30th International Symposium on Pediatric Surgical Research and Update on Newborn Surgery
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sensory innervation of the anal canal and anorectal line in Hirschsprung's disease: histological evidence from mouse models.2017

    • Author(s)
      Takeda M, Miyahara K, Akazawa C, Lane GJ, Yamataka A
    • Organizer
      The 24th International Meeting Colorectal Club
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒルシュスプルング病マウスモデルにおける肛門管の感覚神経とAnorectal line2017

    • Author(s)
      武田昌寛, 宮原克, 赤澤智宏, 山高篤行
    • Organizer
      第74回直腸肛門奇形研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Semaphorin 3A expression following intestinal ischemia/reperfusion injury in Sox10-Venus mice.2016

    • Author(s)
      Takeda M, Miyahara K, Okawada M, Akazawa C, Lane GJ, Yamataka A.
    • Organizer
      The 29th International Symposium on Paediatric Surgical Research
    • Place of Presentation
      Goethe University Frankfurt, Frankfurt, Germany
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Overexpression of aquaporin 4 and the effectiveness of goreisan on the cystic remnants in a case of cervical lympangioma2015

    • Author(s)
      Doi T, Fujiwara N, Miyahara K, Okawada M, Miyano G, Koga H, Yamataka A
    • Organizer
      The 28th International Symposium on Paediatric Surgical Research
    • Place of Presentation
      アイルランド共和国ダブリン市
    • Year and Date
      2015-09-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Three- and four-dimensional analysis of altered behavior of enteric neural crest derived cells in the Hirschsprung's disease mouse model2015

    • Author(s)
      Nakazawa-Tanaka N, Miyahara K, Fujiwara N, Urao M, Akazawa C, Yamataka A
    • Organizer
      The 28th International Symposium on Paediatric Surgical Research
    • Place of Presentation
      アイルランド共和国ダブリン市
    • Year and Date
      2015-09-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased expression of Semaphorin 3A in the Endothelin-B null mouse model of Hirschsprung’s disease.2015

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa N, G.J. Lane, Akazawa C, Yamataka A
    • Organizer
      The 28th International Symposium on Paediatric Surgical Research
    • Place of Presentation
      アイルランド共和国ダブリン市
    • Year and Date
      2015-09-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Key points in trans-anal approach of HD2015

    • Author(s)
      Yamataka A
    • Organizer
      The 11th Annual Meeting of Chinese Association of Pediatric Surgeons
    • Place of Presentation
      中華人民共和国上海市
    • Year and Date
      2015-09-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Endoscopic dextranomer/hyaluronic and injection therapy for vesicoureteral reflux: Japanese experience2015

    • Author(s)
      Yamataka A
    • Organizer
      EUPSA (European Paediatric Surgeon's Association) Annual Congress 2015
    • Place of Presentation
      スロベニア共和国リュブリャナ市
    • Year and Date
      2015-06-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel technical modification for the laparoscopy-assisted transanal pull-through for Hirschsprung’s disease2015

    • Author(s)
      Yamataka A
    • Organizer
      The 22nd International Meeting of the Pediatric Colorectal Club,
    • Place of Presentation
      イタリア共和国ミラノ市
    • Year and Date
      2015-06-14
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Corroboration between pediatric surgeons with specialist knowledge of bowel innervation histopathology and pathologists assists in identifying the transitional segment in Hirschsprung's disease2015

    • Author(s)
      Okawada M, Doi T, Miyano G, Koga H, Lane GJ, Okazaki T, Kobayashi H, Yamataka A
    • Organizer
      The 48th Pacific Association of Pediatric Surgeons
    • Place of Presentation
      大韓民国済州島
    • Year and Date
      2015-05-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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