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Skin regeneration : hair follicle as a model for signal trunsduction

皮肤再生：毛囊作为信号传导的模型

基本信息

批准号：
14370259
负责人：
ITAMI Satoshi
金额：
$ 8.96万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370259/
关键词：
Tissue regeneration Hair follicle Androgen TGF-β1 Stat3 HGF Wound healing Bone marrow stem cell 再生 stat3 毛周期毛乳頭細胞男性型脱毛男性ホルモンレセプター細胞成長因子不死化細胞

项目摘要

One of the typical example of the signal transduction in the human hair cycle progression is androgen-androgen receptor system. In order to know the mode of androgen action in human hair follicles, we developed an in vitro coculture system using DPC and follicular epithelial cells. Androgen significantly stimulated the proliferation of follicular epithelial cells cocultured with beard or axillary DPC, suggesting that these DPC produce androgen-dependent diffusible growth factors. On the other hand, we could identify inhibitory roles of androgen on the growth follicular epithelial cells cocultured with DPC derived from the human bald frontal scalps, when DPC were transfected with the AR expression vector. Androgen-inducible TGF-β1 derived from DPCs plays a central role for the growth suppression.Stat3 plays a crucial role in transducing a signal for the anagen initiation and wound healing. The anagen initiation represents vertical wound healing. Hepatocyte growth factor (HGF) strongly a … More ctivates stat3 in the keratinocytes and promoted migration of keratinocytes. Neutralizing anti-HGF IgG delayed skin wound healing in normal mice. Moreover, exogeneous HGF stimulated cutaneous wound healing in diabetic mice model. HGF would be a potential therapeutic approach for the treatment of chronic skin ulcer.Diabetic foot ulcers with exposed bones commonly result in amputation. Our study that early aggressive debridement of diabetic foot ulcers with exposed bones down to a bleeding vascularized base and then grafting epidermal sheets significantly improves healing and reduces the rate of amputation. The usefulness of bone marrow cells in accelerating wound healing has not been evaluated despite increasing evidence that bone marrow contains mesenchymal stem cells that have multipotentiality to differentiate into various types of cells after they enter the microenvironment of a specific tissue (niche). We founfd that bone marrow cells accelerate the healing of wounds at least in part through their differentiation into wound myofibroblasts. Thus, treatment of wounds with bone marrow cells and a supportive occlusive dressing is effective in promoting the formation of healthy granulation tissue and also for the preparation of an ideal wound bed. Less

雄激素-雄激素受体系统是人类毛发周期信号转导的典型例子之一。为了了解雄激素在人毛囊中的作用方式，我们建立了一个DPC与毛囊上皮细胞体外共培养体系。雄激素显著刺激与胡须或腋窝DPC共培养的滤泡上皮细胞的增殖，表明这些DPC产生雄激素依赖性扩散生长因子。另一方面，我们可以确定雄激素的生长抑制作用的滤泡上皮细胞与DPC来自人秃头额头皮，当DPC转染AR表达载体。DPC来源的雄激素诱导型TGF-β1在生长抑制中起重要作用，Stat 3在传导生长期启动和创伤愈合信号中起重要作用。生长期起始代表垂直伤口愈合。肝细胞生长因子（HGF）是一种强有力的 ...更多信息激活角质形成细胞中的STAT 3并促进角质形成细胞的迁移。中和抗HGF IgG延迟正常小鼠皮肤伤口愈合。此外，外源性HGF促进糖尿病小鼠模型的皮肤伤口愈合。肝细胞生长因子可能是治疗慢性皮肤溃疡的一种潜在方法。糖尿病足溃疡伴骨外露常导致截肢。我们的研究表明，早期积极清创糖尿病足溃疡暴露的骨头下降到出血的血管化基地，然后移植表皮片显着提高愈合，降低截肢率。尽管越来越多的证据表明骨髓中含有间充质干细胞，这些干细胞在进入特定组织的微环境（小生境）后具有分化为各种类型细胞的多潜能性，但尚未评估骨髓细胞在加速伤口愈合中的有用性。我们发现骨髓细胞至少部分通过分化成伤口肌成纤维细胞来加速伤口愈合。因此，用骨髓细胞和支持性封闭敷料治疗伤口可有效促进健康肉芽组织的形成，也可用于制备理想的伤口床。少