Control of hair growth and follicle size by VEGF-mediated angiogenesis
Control of hair growth and follicle size by VEGF-mediated angiogenesis
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DOI：
10.1172/jci11317
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发表时间：
2001-02-01
影响因子：
15.9
通讯作者：
Detmar, M
中科院分区：
文献类型：
--
作者：
Yano, K;Brown, LF;Detmar, M
小鼠毛囊经历明显的循环扩张和收缩，导致对其血管支持的需求迅速变化。我们的研究旨在量化毛囊周围血管形成的循环变化，并表征VEGF在头发生长、血管生成和毛囊循环中的生物学作用。我们发现毛囊周围血管形成在毛发生长阶段（毛发生长初期）显著增加，随后在毛囊生长阶段（毛发脱落期）和毛发休止期（毛发休止期）血管生成血管减少。毛囊周围血管生成在时间和空间上与外根鞘毛囊角质形成细胞上调VEGF mRNA表达相关，而与真皮乳头细胞无关。在毛囊外根鞘角质形成细胞中转基因过表达VEGF，强烈诱导毛囊周围血管化，导致脱毛后毛发再生加速，毛囊和毛轴尺寸增大。相反，用中和性抗vegf抗体进行全身治疗会导致头发生长迟缓和毛囊大小减小。在缺乏功能血管系统的小鼠触须器官培养中，未观察到VEGF治疗或VEGF阻断的影响。这些结果确定了VEGF是毛囊生长和循环的主要媒介，并提供了第一个直接证据，证明改善毛囊血管化可以促进头发生长，增加毛囊和头发大小。
The murine hair follicle undergoes pronounced cyclic expansion and regression, leading to rapidly changing demands for its vascular support. Our study aimed to quantify the cyclic changes of perifollicular vascularization and to characterize the biological role of VEGF for hair growth, angiogenesis, and follicle cycling. We found a significant increase in perifollicular vascularization during the growth phase (anagen) of the hair cycle, followed by regression of angiogenic blood vessels during the involution (catagen) and the resting (telogen) phase. Perifollicular angiogenesis was temporally and spatially correlated with upregulation of VEGF mRNA expression by follicular keratinocytes of the outer root sheath, but not by dermal papilla cells. Transgenic overexpression of VEGF in outer root sheath keratinocytes of hair follicles strongly induced perifollicular vascularization, resulting in accelerated hair regrowth after depilation and in increased size of hair follicles and hair shafts. Conversely, systemic treatment with a neutralizing anti-VEGF antibody led to hair growth retardation and reduced hair follicle size. No effects of VEGF treatment or VEGF blockade were observed in mouse vibrissa organ cultures, which lack a functional vascular system. These results identify VEGF as a major mediator of hair follicle growth and cycling and provide the first direct evidence that improved follicle vascularization promotes hair growth and increases hair follicle and hair size.