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Development of Regeneration Therapy of External Urethral Sphincter based on the Regulation of Cytokine Signaling Pathway

Research Project

Project/Area Number 20591882
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionOita University

Principal Investigator

MIMATA Hiromitsu  Oita University, 医学部, 教授 (60219714)

Co-Investigator(Kenkyū-buntansha) SATO Fuminori  大分大学, 医学部, 准教授 (30305049)
HIRATA Yuji  大分大学, 医学部, 助教 (30295183)
SUMINO YASUHIRO  大分大学, 医学部, 助教 (30325716)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords尿失禁 / 外尿道括約筋 / 骨格筋幹細胞 / サイトカイン / シグナル伝達 / アポトーシス / TGF-β / 腹圧性尿失禁 / 横紋筋幹細胞 / Mostatin / Follistatin / TNF-α / 骨格筋衛星細胞 / 高齢者 / 炎症性サイトカイン
Research Abstract

Fragility of urethral rhabdosphincter is one of the causes for urinary stress incontinence following prostatectomy and in the elderly. To develop new treatment modality of urinary incontinence by regeneration of urethral rhabdosphincter, human satellite cells of urethral rhabdosphincter were separated and cultured to explore the effects of variety of cytokines on them and the signal transduction.
TNF-αdose-dependently suppressed the growth of satellite cells of human urethral rhabdosphincter and induced apoptosis in part, and anti- TNF-αdrugs inhibited these effects. Myostatin, skeletal muscle-specific growth inhibiting factor, was expressed on mRNA and protein levels in satellite cells of human urethral rhabdosphincter. Myostatin suppressed their growth dose-dependently, and its inhibitor, Follistatin, reversed its inhibitory effect.
Regeneration of human urethral rhabdosphincter may be possible with anti-TNF-αdrugs and Myostatin inhibitors and prove a novel therapeutic modality for urinary incontinence.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (35 results)

All 2011 2010 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 5 results) Presentation (23 results)

  • [Journal Article] 外尿道括約筋の再生に関する筋衛星細胞の役割2011

    • Author(s)
      住野泰弘、花田麻里、三股浩光
    • Journal Title

      排尿障害プラクティス 18

      Pages: 317-324

    • Related Report
      2010 Final Research Report
  • [Journal Article] Long-term cryopreservation of pyramidalis muscle specimens as a source of striated muscle stem cells for treatment of post-prostatectomy stress urinary incontinence2011

    • Author(s)
      Sumino Y, Hirata Y, Hanada M, Akita Y, Sato F, Mimata H.
    • Journal Title

      Prostate

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Growth inhibition and apoptosis induction by tumor necrosis factor-alpha in human urethral rhabdosphincter satellite cells.2010

    • Author(s)
      花田麻里, 住野泰弘, 平田裕二, 佐藤文憲, 三股浩光
    • Journal Title

      J Urol 183

      Pages: 2445-2450

    • Related Report
      2010 Final Research Report
  • [Journal Article] The effects of hepatocyte growth factor and insulin-like growth factor-1 on the myogenic differentiation of satellite cells in human urethral rhabdosphincter.2010

    • Author(s)
      住野泰弘, 花田麻里, 平田裕二, 佐藤文憲, 三股浩光
    • Journal Title

      Neurourol Urodyn 29

      Pages: 470-475

    • Related Report
      2010 Final Research Report
  • [Journal Article] 前立腺全摘出術における外科解剖-尿失禁対策2010

    • Author(s)
      住野泰弘、平井健一、佐藤文憲、三股浩光
    • Journal Title

      泌尿器外科 24

      Pages: 27-31

    • Related Report
      2010 Final Research Report
  • [Journal Article] Growth inhibition and apoptosis induction by tumor necrosis factor-alpha in human urethral rhabdosphincter satellite cells.2010

    • Author(s)
      Hanada M, Sumino Y, Hirata Y, Sato F, Mimata H.
    • Journal Title

      J Urol

      Volume: 183 Pages: 2445-2450

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effects of hepatocyte growth factor and insulin-like growth factor-1 on the myogenic differentiation of satellite cells in human urethral rhabdosphincter.2010

    • Author(s)
      Sumino Y, Hanada M, Hirata Y, Sato F, Mimata H.
    • Journal Title

      Neurourol Urodyn.

      Volume: 29 Pages: 470-475

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effects of hepatocyte growth factor and insulin-like growth factor-1 on the myogenic differentiation of satellite cells in human urethral rhabdosphincter2010

    • Author(s)
      Sumino Y, Hanada M, Hirata Y, Sato F, Mimata H
    • Journal Title

      Neurourol Urodyn

      Pages: 470-5

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ヒト外尿道括約筋衛星細胞の増殖制御機構2008

    • Author(s)
      住野泰弘, 平田裕二, 花田麻里, 佐藤文憲, 三股浩光
    • Journal Title

      西日本泌尿器科 70

      Pages: 569-575

    • NAID

      10026146595

    • Related Report
      2010 Final Research Report
  • [Journal Article] ヒト外尿道括約筋衛星細胞の増殖制御機構2008

    • Author(s)
      住野泰弘, 他
    • Journal Title

      西日本泌尿器科 70

      Pages: 569-575

    • NAID

      10026146595

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term cryopreservation of pyramidalis muscle specimens as a source of striated muscle stem cells for treatment of post-prostatectomy stress urinary incontinence.

    • Author(s)
      Sumino Y, Hirata Y, Hanada M, Akita Y, Sato F, Mimata H
    • Journal Title

      Prostate in press.

    • Related Report
      2010 Final Research Report
  • [Journal Article] SOCS1による炎症性発癌の制御

    • Author(s)
      花田俊勝, 三股浩光
    • Journal Title

      臨床免疫アレルギー科

    • Related Report
      2010 Final Research Report
  • [Presentation] プロテオミクスによる外尿道括約筋特異蛋白の同定2011

    • Author(s)
      秋田泰之
    • Organizer
      第20回泌尿器科分子・細胞研究会
    • Place of Presentation
      津
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト外尿道括約筋におけるMyostatinの発現と機能解析2010

    • Author(s)
      秋田泰之
    • Organizer
      第7回泌尿器科再建再生研究会
    • Place of Presentation
      札幌市
    • Year and Date
      2010-06-09
    • Related Report
      2010 Final Research Report
  • [Presentation] IGF-I局所投与はラット外尿道括約筋の肥大を誘導する2010

    • Author(s)
      秋田泰之
    • Organizer
      第7回泌尿器科再建再生研究会
    • Place of Presentation
      札幌市
    • Year and Date
      2010-06-09
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト外尿道括約筋におけるMyostatinの発現と機能解析2010

    • Author(s)
      秋田泰之
    • Organizer
      第98回日本泌尿器科学会総会
    • Place of Presentation
      盛岡市
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト外尿道括約筋および肛門挙筋におけるトランスクリプトーム解析2010

    • Author(s)
      花田麻里
    • Organizer
      第98回日本泌尿器科学会総会
    • Place of Presentation
      盛岡市
    • Related Report
      2010 Final Research Report
  • [Presentation] Long-term preservation of pyramidalis muscle specimens as a source of striated muscle stem cells for treatment of post-prostatectomy stress urinary incontinence.2010

    • Author(s)
      Yasuhiro Sumino
    • Organizer
      American Urology Association 2010
    • Place of Presentation
      San Francisco, CA, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] Myostatin Inhibits Growth of Satellite Cells in Human Urethral Rhabdosphincter via Phosphorylation of Smad-22010

    • Author(s)
      Yasuhiro Sumino
    • Organizer
      Joint Annual Meeting of the International Continence Society and the International Urogynecological Association
    • Place of Presentation
      Toronto, Canada
    • Related Report
      2010 Annual Research Report
  • [Presentation] 外尿道括約筋の再生療法2009

    • Author(s)
      三股浩光
    • Organizer
      第22回日本老年泌尿器科学会
    • Place of Presentation
      京都
    • Year and Date
      2009-05-09
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Growth Inhibition and Apoptosis Induction by Tumor Necrosis Factoralpha in Human Urethral Rhabdosphincter Satellite Cells2009

    • Author(s)
      Mari Hanada
    • Organizer
      American Urology Association 2009
    • Place of Presentation
      Chicago, Illinois, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト女性外尿道括約筋における横紋筋線維型の検討2009

    • Author(s)
      住野泰弘
    • Organizer
      第97回日本泌尿器科学会総会
    • Place of Presentation
      岡山
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト外尿道括約筋と肛門挙筋のプロテオーム解析2009

    • Author(s)
      住野泰弘
    • Organizer
      第16回日本排尿機能学会
    • Place of Presentation
      福岡
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト外尿道括約筋衛星細胞における遊走と浸潤いついての検討2008

    • Author(s)
      平田裕二
    • Organizer
      第5回泌尿器科再建再生研究会
    • Place of Presentation
      仙台
    • Year and Date
      2008-06-27
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] LIF(白血病阻害因子)はヒト外尿道括約筋筋芽細胞の遊走活性を誘導する2008

    • Author(s)
      平田裕二
    • Organizer
      第96回日本泌尿器科学会総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] The effects of hepatocyte growth factor and insulin-like growth factor-1 on the myogenic differentiation of satellite cells in human urethral rhabdosphincter2008

    • Author(s)
      Yasuhiro Sumino
    • Organizer
      AUA
    • Place of Presentation
      Orland, Florida, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト外尿道括約筋衛星細胞におけるTNF-αのアポトーシス誘導2008

    • Author(s)
      花田麻里
    • Organizer
      第17回日本アポトーシス研究会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト外尿道括約筋衛星細胞における遊走と浸潤いついての検討2008

    • Author(s)
      平田裕二
    • Organizer
      第15回日本排尿機能学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト外尿道括約筋衛星細胞においてTNF-αはTNF受容体を介してアポトーシスを誘導する2008

    • Author(s)
      花田麻里
    • Organizer
      第15回日本排尿機能学会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Growth Inhibition and Apoptosis induction by TNF-α in Satellite cells of Human Urethral Rhabdosphincte2008

    • Author(s)
      花田麻里
    • Organizer
      第60回日本泌尿器科学会西日本総会
    • Place of Presentation
      北九州市
    • Related Report
      2010 Final Research Report
  • [Presentation] The effects of hepatocyte growth factor and insulin-like growth factor-1 on the myogenic differentiation of satellite cellsin human urethral rhabdosphincter2008

    • Author(s)
      Yasuhiro Sumino, Hiromitsu Mimata
    • Organizer
      AUA
    • Place of Presentation
      Orland, Florida, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒト外尿道括約筋衛星細胞におけるTNF-αのアポトーシス誘導2008

    • Author(s)
      花田麻里, 平田裕二, 住野泰弘, 山崎六志, 佐藤文憲, 三股浩光
    • Organizer
      第17回日本アポトーシス研究会
    • Place of Presentation
      京都市
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒト外尿道括約筋衛星細胞における遊走と浸潤いついての検討2008

    • Author(s)
      平田裕二, 花田麻里, 住野泰弘, 佐藤文憲, 三股浩光
    • Organizer
      第15回日本排尿機能学会
    • Place of Presentation
      東京都大手町
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒト外尿道括約筋衛星細胞においてTNF-αはTNF受容体を介してアポトーシスを誘導する2008

    • Author(s)
      花田麻里, 平田裕二, 住野泰弘, 山崎六志, 佐藤文憲, 三股浩光
    • Organizer
      第15回日本排尿機能学会
    • Place of Presentation
      東京都大手町
    • Related Report
      2008 Annual Research Report
  • [Presentation] Growth Inhibition and Apoptosis induction by TNF-α in Satellite cells of Human Urethral Rhabdosphincter2008

    • Author(s)
      Mari Hanada, Yuji Hirata, Yasuhiro Sumino, Mutsushi Yamasaki, Fuminori Sato, Hiromitsu Mimata
    • Organizer
      第60回日本泌尿器科学会西日本総会
    • Place of Presentation
      北九州市
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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