An important role of cutaneous lymphatic vessels in coordinating and promoting anagen hair follicle growth

PLoS One. 2019 Jul 25;14(7):e0220341. doi: 10.1371/journal.pone.0220341. eCollection 2019.

Abstract

The lymphatic vascular system plays important roles in the control of tissue fluid homeostasis and immune responses. While VEGF-A-induced angiogenesis promotes hair follicle (HF) growth, the potential role of lymphatic vessels (LVs) in HF cycling has remained unknown. In this study, we found that LVs are localized in close proximity to the HF bulge area throughout the postnatal and depilation-induced hair cycle in mice and that a network of LVs directly connects the individual HFs. Increased LV density in the skin of K14-VEGF-C transgenic mice was associated with prolongation of anagen HF growth. Conversely, HF entry into the catagen phase was accelerated in K14-sVEGFR3 transgenic mice that lack cutaneous LVs. Importantly, repeated intradermal injections of VEGF-C promoted hair growth in mice. Conditioned media from lymphatic endothelial cells promoted human dermal papilla cell (DPC) growth and expression of IGF-1 and alkaline phosphatase, both activators of DPCs. Our results reveal an unexpected role of LVs in coordinating and promoting HF growth and identify potential new therapeutic strategies for hair loss-associated conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Dermis / cytology
  • Dermis / growth & development
  • Female
  • Hair Follicle / cytology
  • Hair Follicle / growth & development*
  • Hair Follicle / metabolism
  • Hair Removal
  • Humans
  • Lymphangiogenesis / genetics
  • Lymphangiogenesis / physiology*
  • Lymphatic Vessels / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Regeneration / genetics
  • Skin / cytology
  • Skin / growth & development*
  • Skin / metabolism
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor Receptor-3 / genetics

Substances

  • Vascular Endothelial Growth Factor C
  • vascular endothelial growth factor C, mouse
  • Vascular Endothelial Growth Factor Receptor-3

Grant support

This work was supported by Swiss National Science Foundation grants 31003A-130627 and 310030B-185392, Advanced European Research Council grant LYVICAM and Leducq Transatlantic Network of Excellence on Lymph Vessels in Obesity and Cardiovascular Disease (11CVD03).