Skin regeneration : hair follicle as a model for signal trunsduction

雄激素-雄激素受体系统是人类毛发周期过程中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模式，我们建立了DPC与毛囊上皮细胞体外共培养体系。雄激素显著刺激了与胡须或腋窝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，当AR表达载体转染人秃头DPC时，我们可以发现雄激素对DPC与人秃头DPC共培养的滤泡上皮细胞的生长有抑制作用。雄激素诱导的TGF-β1来源于DPCs，在抑制生长中起核心作用。Stat3在生长期启动和伤口愈合的信号转导中起着至关重要的作用。生长素起始表示垂直创面愈合。肝细胞生长因子（HGF）强烈激活角化细胞中的stat3，促进角化细胞的迁移。中和抗hgf IgG延缓正常小鼠皮肤创面愈合。此外，外源性HGF还能促进糖尿病小鼠皮肤创面愈合。HGF是治疗慢性皮肤溃疡的一种潜在的治疗方法。糖尿病足溃疡与暴露的骨头通常导致截肢。我们的研究表明，早期积极清创的糖尿病足溃疡暴露的骨头到出血血管的基础，然后移植表皮片显著提高愈合和减少截肢率。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（生态位）的微环境后具有多能分化为各种类型的细胞，但骨髓细胞在加速伤口愈合方面的有用性尚未得到评估。我们发现骨髓细胞至少在一定程度上是通过分化成伤口肌成纤维细胞来加速伤口愈合的。因此，用骨髓细胞和支持性闭塞敷料治疗伤口在促进健康肉芽组织的形成和制备理想的伤口床方面是有效的。少

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