权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Signal transduction in human hair follicles

人类毛囊中的信号转导

基本信息

批准号：
12670819
负责人：
ITAMI Satoshi
金额：
$ 1.92万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670819/
关键词：
Tissue regeneration Hair cycle Stem cell Dermal papilla cell Androgen receptor Growth factor STAT3 TGF-β 毛 PKC PI3K

项目摘要

One of the typical example of the signal transduction in the cell 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 contrary, 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.We previously established keratinocyte-specific Stat3-disrupted mice, and found that Stat3 is required for anagen progression in the hair cycle. Anagen was successfully induced even in Stat3-disrupted mice by topical application of PMA. PMA stimulated the migration of Stat3-disrupted keratinocytes in vitro. Both Stat3-dependent and independent migration of keratinocytes was inhibited by wortmannin. Therefore, anagen is mediated by at least two distinct signaling pathways : Stat3-dependent pathway for spontaneous hair cycling and Stat3-independent (probably PKC-dependent) pathway for exogenously induced hair cycling, whereas both pathways require PI3K activation.

雄激素-雄激素受体系统是细胞内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，我们建立了一种以DPC和毛囊上皮细胞为材料的体外共培养系统。雄激素显著刺激与胡须或腋窝DPC共培养的卵泡上皮细胞的增殖，提示这些DPC产生雄激素依赖的扩散性生长因子。相反，将AR表达载体导入DPC后，我们发现雄激素对与DPC共培养的毛囊上皮细胞生长有抑制作用。DPC来源的雄激素诱导的转化生长因子-STAT1在生长抑制中起核心作用。我们以前建立了角质形成细胞特异性β3干扰的小鼠，并发现STAT3在毛发周期的生长期进展中是必需的。即使在STAT3干扰的小鼠中，局部应用PMA也能成功地诱导生长期。PMA在体外刺激STAT3破坏的角质形成细胞迁移。Wortmannin抑制角质形成细胞的STAT3依赖性迁移和非依赖性迁移。因此，ANAGE至少由两条不同的信号通路介导：一条是STAT3依赖的自发毛发周期通路，另一条是外源诱导毛发周期的STAT3非依赖性(可能是PKC依赖的)通路，而这两条通路都需要PI3K的激活。