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

基于细胞因子信号通路调控的尿道外括约肌再生治疗进展

• 批准号: 20591882
• 负责人: MIMATA Hiromitsu
• 金额: $ 2.91万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591882/
• 关键词: 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

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.

尿道胸肌的脆弱性是前列腺切除术和年龄较大后尿应力尿失禁的原因之一。 To develop new treatment modality of urinary incontinence by regeneration of urethral rhabdostrophincter, human satellite cells of urethral rhabdostrophincter 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 rhabdostrophincter and induced apoptosis in part, and抗TNF-α药物抑制了这些作用。肌抑制素，骨骼肌特异性生长抑制因子，在人类尿道透射性手术的卫星细胞中的mRNA和蛋白质水平上表达。 Myostatin抑制其生长剂量依赖性，其抑制剂Follistatin逆转了其抑制作用。抗TNF-α药物和肌抑制素抑制剂可能可以使用人类尿道尖锐的肌营养素再生，并证明尿液尿失禁的新型治疗方式。

项目成果

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

TNF-α通过TNF受体诱导人尿道外括约肌卫星细胞凋亡

• 发表时间: 2008
• 作者: 窪田泰江;橋谷光;小島祥敬;佐々木昌一;早瀬麻沙;鈴木光;郡健二郎;花田麻里
• 通讯作者: 花田麻里

Growth Inhibition and Apoptosis induction by TNF-α in Satellite cells of Human Urethral Rhabdosphincter

TNF-α对人尿道横纹括约肌卫星细胞的生长抑制和凋亡诱导

• 发表时间: 2008
• 作者: Mari Hanada;Yuji Hirata;Yasuhiro Sumino;Mutsushi Yamasaki;Fuminori Sato;Hiromitsu Mimata
• 通讯作者: Hiromitsu Mimata

前立腺全摘出術における外科解剖-尿失禁対策

根治性前列腺切除术的手术解剖学——尿失禁措施

• 发表时间: 2010
• 期刊: 泌尿器外科 24
• 作者: 住野泰弘;平井健一;佐藤文憲;三股浩光
• 通讯作者: 三股浩光

プロテオミクスによる外尿道括約筋特異蛋白の同定

通过蛋白质组学鉴定尿道外括约肌特异性蛋白

• 发表时间: 2011
• 作者: 土田孝之;井上千尋;大竹裕子;羽根田破;小林英樹;宮本達也;武田正之;秋田泰之
• 通讯作者: 秋田泰之

ヒト外尿道括約筋におけるMyostatinの発現と機能解析

Myostatin在人尿道外括约肌中的表达及功能分析

• 发表时间: 2010
• 作者: Yasui T;Itoh Y;et al.;秋田泰之
• 通讯作者: 秋田泰之