Identification of Origin and Elucidation of Growth and Differetniation Mechanism of Satellite Cells in Human Urethral Rhabdosphincter

人尿道横纹括约肌卫星细胞来源的鉴定及生长和分化机制的阐明

基本信息

批准号：
17591687
负责人：
MIMATA Hiromistu
金额：
$ 2.5万
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：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Objective : Urethral rhabdosphincter is the most important tissue for preservation of urinary continence, and its injury and/or decrease due to aging and prostate surgery induced stress urinary incontinence. This study was performed to clarify and culture satellite cells in human urethral rhabdosphincter for the elucidation of growth and differentiation mechanism and development of new therapeutic modality for urethral rhabdosphincter regeneration.Materials and Method : Human urethral rhabdosphincter was obtained from patients who underwent radical prostatectomy or radical cystoprostatectomy. After the specimens were treated with collagenase and cultured, satellite cells in human urethral rhabdosphincter were isolated by MACS technique using anti-NCAM antibody conjugated with microbeads. Isolated satellite cells were confirmed as striated muscle origin by immunocytochemistry with anti-Myf-5 and anti-MyoD antibodies, and they were transfected with SV40 T antigen to obtain longevity.Results and Conclusion : Satellite cells of human urethral rhabdosphincter produced HGF and IGF-I at mRNA and protein levels, which stimulated their growth. HGF and IGF-I activated MAPK and PI3-K signal transduction in satellite cells of human urethral rhabdosphincter, respectively.Human urethral rhabdosphincter is reported to decrease due to apotosis with aging. In this study, TNF-α induced apoptosis by dose-dependent fashion in satellite cells of human urethral rhabdosphincter for the first time. Inhibitors of TNF-α may protect human urethral rhabdospincter from reduction with aging and be useful for the treatment and prevention of stress urinary incontinence in elderly.

目的：尿道横纹肌是保存尿道的最重要的组织，其损伤和/或由于衰老和前列腺手术引起的损伤和/或减少会诱导的压力尿失禁。进行这项研究是为了澄清和培养人类尿道突破症中的卫星细胞，以阐明生长和分化机制，以及用于尿道尖体再生的新治疗方式的新治疗方式。人材料和方法。在用胶原酶处理样品并培养的样品后，使用与微片共轭的抗NCAM抗体分离人类尿道纹状蛋白的卫星细胞。通过抗Myf-5和抗MYOD抗体的免疫细胞化学将孤立的卫星细胞确认为肌肉的起源，并用SV40 t抗原翻译以获得寿命和结论：人尿中rhabdostrophterpter raptropterpropter the the hgff and igf-i的卫星细胞，并在MRNA中产生了rhabdostropterpter的生长。 HGF和IGF-1分别激活的MAPK和PI3-K信号转导了人类尿道胸腺骨蛋白的卫星细胞中。据报道，由于衰老的凋亡而导致的人类尿道尖锐的透明透明脂质量会降低。在这项研究中，TNF-α首次在人类尿道纹章的卫星细胞中通过剂量依赖性方式诱导凋亡。 TNF-α的抑制剂可以保护人类尿道透明挥手挥舞者免受衰老的减少，并可用于治疗和预防较早的应激尿液尿失禁。