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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Accelerated hair regrowth and increased follicle size in VEGF transgenic...
Accelerated hair regrowth and increased follicle size in VEGF transgenic mice. VEGF transgenic mice showed more and thicker hair at day 11 after depilation (b), as compared with wild-type littermates (a). Histological analysis of H&E-stained paraffin sections demonstrates increased size of hair bulbs in VEGF transgenic mice at day 12 (d) and day 15 (f) after depilation, as compared with wild-type (WT) mice at day 12 (c) and day 15 (e). Scale bars = 100 μm. Hair bulbs in VEGF transgenic mice, measured at the level of the largest diameter, were more than 35% thicker than in wild-type mice at day 12 (g) and day 15 (j) after depilation. Quantitative analysis of CD31 stains revealed that perifollicular vascularization, assessed as average vessel size (h, day 12; k, day 15) or relative vessel area (i, day 12; l, day 15), was significantly increased in VEGF transgenic mice during late anagen. Data are expressed as means ± SD. AP < 0.01, BP < 0.001, two-sided unpaired Student’s t test.