Manipulation of outer root sheath cell survival perturbs the hair-growth cycle
Manipulation of outer root sheath cell survival perturbs the hair-growth cycle
复制标题
DOI：
10.1093/emboj/18.13.3596
复制
发表时间：
1999-07-01
期刊：
影响因子：
11.4
通讯作者：
Thompson, CB
中科院分区：
文献类型：
--
作者：
Pena, JC;Kelekar, A;Thompson, CB
在角蛋白14启动子控制下过表达抗凋亡基因bcl-x(L)的转基因小鼠的毛发比非转基因同窝小鼠明显短。毛发长度的不足与毛发生长初期（毛发周期的生长期）持续时间的缩短相关，在成年动物中也观察到毛发生长终期（毛发周期的静止期）的延长。在发育中的毛球中，仅在外根鞘（ORS）细胞中观察到bcl-x（L）转基因表达，Bcl-x（L）表达增强了用凋亡刺激处理的ORS细胞的存活率。结果表明，在生长期期间防止 ORS 细胞凋亡会导致祖细胞定型/增殖更快终止，而在休止期期间 ORS 细胞的存活率增加会延迟新毛发周期的开始。 ORS 细胞产生成纤维细胞生长因子 5 (FGF-5)，它以旁分泌方式发挥作用，终止生长期期间的前体细胞分裂。bcl-x(L) 转基因小鼠的短毛表型在 FGF-5 缺陷小鼠中显着逆转。因此，ORS细胞产生的生长抑制因子可能提供一种通过细胞存活来调节毛发生长周期的机制。
Transgenic mice that overexpress the anti-apoptotic gene bcl-x(L) under the control of the keratin 14 promoter have significantly shorter hair than non-transgenic littermates. The deficit in hair length correlated with a decrease in the duration of anagen, the growth phase of the hair cycle, A prolongation in telogen, the resting phase of the hair cycle, was also observed in adult animals. Zn the developing hair bulb, bcl-x(L) transgene expression was observed exclusively in the outer root sheath (ORS) cells, Bcl-x(L) expression enhanced the survival of ORS cells treated with apoptotic stimuli. The results suggest that preventing the apoptotic death of ORS cells during anagen leads to a more rapid termination of progenitor cell commitment/proliferation, while the increased survival of ORS cells during telogen delays the initiation of a new hair cycle. ORS cells produce fibroblast growth factor-5 (FGF-5), which acts in a paracrine fashion to terminate precursor cell division during anagen, The short hair phenotype of bcl-x(L) transgenic mice was substantially reversed in FGF-5-deficient mice. Thus, the production of growth inhibitory factors by ORS cells may provide a mechanism through which the hair-growth cycle is regulated by cell survival.