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Functional analysis of the PI3K/Akt signaling pathway during the mammalian inner ear development and its application for regenerative medicine

Research Project

Project/Area Number 23592496
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionJuntendo University

Principal Investigator

MURATA junko  順天堂大学, 医学部, 准教授 (80332740)

Co-Investigator(Kenkyū-buntansha) KIMURA Thoru  北里大学, 理学部, 教授 (50280962)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsPi3K/Aktシグナル伝達系 / PTEN / PTEN ckoマウス / ほ乳類 / 内耳発生 / 感覚上皮予定領域 / 有毛細胞 / PI3K/Aktシグナル径路 / 蝸牛 / PI3K/Aktシグナル経路 / PTEN cko マウス / convergent extension / PI3/Aktシグナル伝達系
Research Abstract

PTEN, a product of a tumor suppressor gene, inhibits the PI3K/Akt pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate. We tried to elucidate the functions of PTEN during mammalian cochlear development by deleting PTEN conditionally in the mouse inner ear.
In PTEN-conditional knockout (cko) mutant cochlea, the diameter of cochlear ducts was increased and the cell proliferation continued till the later stage outside of the prosensory region. Extra rows of OHCs and IHCs were observed, whereas the average length of the cochlear ducts was shorter than that of the control mice. The expression patterns of early prosensory markers were almost same between the PTEN-CKO and the control mice. However, the hair cell differentiation was accelerated in the PTEN-CKO cochleae. The results indicate that PTEN may regulate the cell differentiation and proliferation after the prosensory determination, and contribute to the convergent extension of the cochlear duct.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (25 results)

All 2014 2013 2012 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (18 results) Book (2 results)

  • [Journal Article] Spatio-temporal expression of TRPM4 in the mouse cochlea2014

    • Author(s)
      Sakuraba M, Murata J (Corresponding author), Teruyama R, Kamiya K, Yamaguchi J, Okano H, Uchiyama Y
    • Journal Title

      Ikeda K J Neurosci Res

      Volume: (Epub ahead of print) Issue: 10 Pages: 1409-1418

    • DOI

      10.1002/jnr.23410

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of TRPM4 in the mouse cochlea and its putative roles in the potassium ion transport and the inner hair cell repolarization2014

    • Author(s)
      Junko Murata, Mayumi Sakuraba, Ryoichi Teruyama, Kazusaku Kamiya, Junji Yamaguchi, Hideyuki Okano, Yasuo Uchiyama, Katsuhisa Ikeda
    • Journal Title

      Abstract of the Annual Midwinter Meeting of the Association for Research in Otolaryngology

      Volume: 37 Pages: 506-506

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subclassification of chronic rhinosinusitis with nasal polyps based on eosinophil and neutrophil2013

    • Author(s)
      Ikeda K, Shiozawa A, Ono N, Kusunoki T, Hirotsu M, Honnma H, Saitoh T, Murata J
    • Journal Title

      Laryngoscope

      Volume: 123(11) Pages: 1-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 周囲構造への浸潤がみられた副鼻腔真菌症の2例2012

    • Author(s)
      宇野敦彦、村田潤子、西池季隆、西村洋、今井貴夫、太田有美、池田勝久、猪原秀典
    • Journal Title

      耳鼻臨床

      Volume: 1105 : 1 Pages: 21-26

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 鼻副鼻腔内反性乳頭腫32例の検討2011

    • Author(s)
      津田武、西池季隆、川島貴之、村田潤子、喜井正士、田村学、猪原秀典
    • Journal Title

      耳鼻臨床

      Volume: 104 : 6 Pages: 427-433

    • NAID

      10028222978

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Expression of TRPM4 in the mouse cochlea and its putative roles in the potassium ion transport and the inner hair cell repolarization2014

    • Author(s)
      Murata J, Sakuraba M, Teruyama R, Kamiya K, Yamaguchi J, Okano H, Uchiyama Y, Ikeda K
    • Organizer
      (The 37th Annual Midwinter Meeting of ARO
    • Place of Presentation
      Manchester Grand Hyatt, San Diego, CA, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Expression of TRPM4 in the mouse cochlea and its putative roles in the potassium ion transport and the inner hair cell repolarization2014

    • Author(s)
      Junko Murata, Mayumi Sakuraba, Ryoichi Teruyama, Kazusaku Kamiya, Junji Yamaguchi, Hideyuki Okano, Yasuo Uchiyama, Katsuhisa Ikeda
    • Organizer
      The 37th Annual Midwinter Meeting of the Association for Research in Otolaryngology
    • Place of Presentation
      Manchester Grand Hyatt, San Diego, CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] PTEN Plays Multiple Roles by Regulating Both PI3K/Akt and MEK/Erk Signaling Pathway During the Mammalian Inner Ear Development2013

    • Author(s)
      Murata J, Sakuraba M, Kimura T, Suzuki A, Mak T, Okano H, Nakano T, Ikeda K
    • Organizer
      The 36th Annual Midwinter Meeting of ARO
    • Place of Presentation
      Baltimore Marriott Waterfront Hotel, Baltimore, Maryland)
    • Related Report
      2013 Final Research Report
  • [Presentation] 内耳発生におけるTRPM4の発現変化とEP形成との関連について2013

    • Author(s)
      村田潤子、城所淑信、松岡理奈、池田勝久順天堂大学医学部耳鼻咽喉科
    • Organizer
      第13回日本耳科学会総会・学術講演会
    • Place of Presentation
      宮崎シーガイアコンベンションセンター、宮崎
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌抑制遺伝子PTENの哺乳類内耳発生における役割の検討2013

    • Author(s)
      村田潤子、池田勝久順天堂大学医学部耳鼻咽喉科
    • Organizer
      第114回日本耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      ロイトン札幌・ホテル札幌芸文館、札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] ESS後にアスピリン減感作療法を併用したAIAの臨床経過と末梢リンパ球上のサイトカイン発現について2013

    • Author(s)
      村田潤子、本間博友、齋藤達矢、西村将彦、小野倫嗣、沖崎貴子、岡田弘子、池田勝久順天堂大学医学部耳鼻咽喉科
    • Organizer
      第52回日本鼻科学会総会・学術講演会
    • Place of Presentation
      福井フェニックスプラザ、福井
    • Related Report
      2013 Final Research Report
  • [Presentation] 癌抑制遺伝子PTENの哺乳類内耳発生における役割の検討2013

    • Author(s)
      村田 潤子、池田 勝久
    • Organizer
      第114回日本耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      ロイトン札幌・ホテル札幌芸文館、札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] 内耳発生におけるTRPM4の発現変化とEP形成との関連について2013

    • Author(s)
      村田 潤子、城所 淑信、松岡理奈、池田 勝久
    • Organizer
      第13回日本耳科学会総会・学術講演会
    • Place of Presentation
      宮崎シーガイアコンベンションセンター、宮崎
    • Related Report
      2013 Annual Research Report
  • [Presentation] PTEN Plays Multiple Roles by Regulating Both PI3K/Akt and MEK/Erk Signaling Pathway During the Mammalian Inner Ear Development2013

    • Author(s)
      Junko Murata, Mayumi Sakuraba, Tohru Kimura, Akira Suzuki, Tak Mak, Hideyuki Okano, Toru Nakano, Katsuhisa Ikeda
    • Organizer
      The 36th Annual Midwinter Meeting of the Association for Research in Otolaryngology
    • Place of Presentation
      Baltimore Marriott Waterfront Hotel, Baltimore, Maryland
    • Related Report
      2012 Research-status Report
  • [Presentation] The Expression of Fbxo 45 in the Developing Inner Ear2012

    • Author(s)
      Sakuraba M, Murata J, Tada H, Shibata S, Kamiya K, Okano H, Ikeda K
    • Organizer
      35^<th> ARO MidWinter Meeting
    • Place of Presentation
      The Manchester Grand Hyatt Hotel San Diego, California, USA)
    • Related Report
      2013 Final Research Report
  • [Presentation] ESS後にアスピリン減感作療法を施行したAIAの予後について2012

    • Author(s)
      村田潤子、斉藤達矢、西村将彦、本間博友、沖崎貴子、池田勝久、熱田了、高橋和久
    • Organizer
      第51回日本鼻科学会総会・学術講演会
    • Place of Presentation
      幕張メッセ、千葉
    • Related Report
      2013 Final Research Report
  • [Presentation] The Expression of Fbxo45 in the Developing Inner Ear2012

    • Author(s)
      Junko Murata, Mayumi Sakuraba, Hirobumi Tada, Shinsuke Shibata, et al.
    • Organizer
      35th ARO MidWinter Meeting
    • Place of Presentation
      The Manchester Grand Hyatt Hotel&#8232;San Diego, California, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] 内視鏡手術後に再燃したASA合併難治性慢性副鼻腔炎に対するアスピリン減感作療法の経験2011

    • Author(s)
      村田潤子、飯塚崇、斉藤達矢、笠井美里、岡田弘子、熱田了、高橋和久、池田勝久
    • Organizer
      アスピリン不耐症・難治性喘息研究会2011
    • Place of Presentation
      AP品川(東京都品川区)
    • Year and Date
      2011-11-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 内視鏡手術後に再燃したASA合併難治性慢性副鼻腔炎に対するアスピリン減感作療法の経験2011

    • Author(s)
      村田潤子
    • Organizer
      第60甲斐御茶の水耳鼻咽喉・頭頸科治療研究会
    • Place of Presentation
      東京
    • Year and Date
      2011-04-14
    • Related Report
      2013 Final Research Report
  • [Presentation] 再生医療への応用を指向した内耳発生研究:内耳感覚上皮前駆細胞の増殖と分化に関与するシグナル伝達経路の解明2011

    • Author(s)
      村田潤子、神谷和作、岡野栄之、池田勝久
    • Organizer
      第21回日本耳科学会総会・学術講演会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Related Report
      2013 Final Research Report
  • [Presentation] Sternberg's canalからの髄膜瘤に伴う特発性髄液漏の2症例とその治療経験2011

    • Author(s)
      村田潤子、畠将晃、飯塚崇、笠井美里、岡田弘子、本間博友、小野倫嗣、広津幹夫、楠威志、池田勝久
    • Organizer
      第73回耳鼻咽喉科臨床学会総会・学術講演会
    • Place of Presentation
      松本文化会館(長野県松本市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 内視鏡下に経上顎洞的に開放し得た側頭下窩粘液嚢胞の一例2011

    • Author(s)
      村田潤子、飯塚崇、加瀬香、笠井美里、小野倫嗣、楠威志、池田勝久
    • Organizer
      第112回日本耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Final Research Report
  • [Presentation] 再生医療への応用を指向した内耳発生研究:内耳感覚上皮前駆細胞の増殖と分化に関与するシグナル伝達経路の解明

    • Author(s)
      村田 潤子、神谷 和作、岡野 栄之、池田 勝久
    • Organizer
      第21回日本耳科学会総会・学術講演会
    • Place of Presentation
      沖縄コンベンションセンター、沖縄県
    • Related Report
      2011 Research-status Report
  • [Book] Notch Signaling and the Developing Inner ear in'Notch Signaling in Embryology and Cancer'(Chapter 12) edited by Jorg Reichrath and Sandra Reichrath2012

    • Author(s)
      Murata J, Ikeda K, and Okano H
    • Publisher
      Landes Bioscience and Springer
    • Related Report
      2013 Final Research Report
  • [Book] Chapter 12 ‘Notch Signaling and the Developing Inner Ear’ from Notch Signaling in Embryology and Cancer, edited by Jorg Reichrath and Sandra Reichrath2012

    • Author(s)
      Junko Murata, Katsuhisa Ikeda,
    • Total Pages
      13
    • Publisher
      Landes Bioscience and Springer Science + Business Media
    • Related Report
      2011 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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