Control of hair growth and follicle size by VEGF-mediated angiogenesis
Kiichiro Yano, … , Lawrence F. Brown, Michael Detmar
Kiichiro Yano, … , Lawrence F. Brown, Michael Detmar
Published February 15, 2001
Citation Information: J Clin Invest. 2001;107(4):409-417. https://doi.org/10.1172/JCI11317.
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Control of hair growth and follicle size by VEGF-mediated angiogenesis

Abstract

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.

Authors

Kiichiro Yano, Lawrence F. Brown, Michael Detmar

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Figure 1

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Pronounced vascular changes during the induced murine hair cycle. (a and...
Pronounced vascular changes during the induced murine hair cycle. (a and b) CD31 immunostains demonstrate a marked increase in perifollicular vascularization during late anagen (day 12, a) with subsequent regression of blood vessels during catagen and telogen (day 22, b). (c) Detection of proliferating endothelial cells (arrowheads) in perifollicular vessels during the anagen growth phase. Proliferating cells are depicted in red (BrdU), endothelial cells in green (CD31). (d) Endothelial cell apoptosis (arrowheads) was detectable in perifollicular vessels during the catagen involution phase. Apoptotic cells are depicted in green, endothelial cells in red. Asterisks indicate the location of hair bulbs. Scale bars = 100 μm. Computer-assisted image analysis revealed significant cyclic changes of relative areas covered by vessels (e) and of the average vessel size (f), with a more than fourfold increase during anagen (P < 0.001) and a decrease to early anagen levels during catagen and telogen. (g) Vessel densities were not significantly changed during the hair cycle. Vascular changes were temporally associated with cyclic changes of hair follicle size (i) and dermal thickness (j), but not of epidermal thickness (h). H&E-stained sections were evaluated as described in Methods. Data are expressed as means ± SD of three independent experiments. AP < 0.05; BP < 0.01; CP < 0.001 (increase over early anagen). EA, early anagen; MA, mid-anagen; LA, late anagen; C, catagen; T, telogen; D, day.