The Glypican-1/HGF/C-Met and Glypican-1/VEGF/VEGFR2 Ternary Complexes Regulate Hair Follicle Angiogenesis.

Charlie Colin-Pierre,Solène Mine,Romain Rivet,Christine Jeanmaire,François-Xavier Maquart,Stéphane Brézillon,Nicolas Berthélémy,Louis Danoux,Laurent Ramont,Vincent Bardey,Nicolas Belloy

doi:10.3389/fcell.2021.781172

Abstract

The hair renewal involves changes in the morphology of the hair follicle and its micro-vascularization. In alopecia, the hair cycle is accelerated, resulting in the formation of thinner and shorter hair. In addition, alopecia is associated with a decrease in the micro-vascularization of the hair follicles. In this study, the role of glypicans (GPCs) was analyzed in the regulation of the angiogenesis of human dermal microvascular endothelial cells (HDMEC). The analysis of glypican gene expression showed that GPC1 is the major glypican expressed by human keratinocytes of outer root sheath (KORS), human hair follicle dermal papilla cells (HHFDPC) and HDMEC. KORS were demonstrated to secrete VEGF and HGF. The HDMEC pseudotube formation was induced by KORS conditioned media (KORSCM). It was totally abrogated after GPC1 siRNA transfection of HDMEC. Moreover, when cleaved by phospholipase C (PLC), GPC1 promotes the proliferation of HDMEC. Finally, GPC1 was shown to interact directly with VEGFR2 or c-Met to regulate angiogenesis induced by the activation of these receptors. Altogether, these results showed that GPC1 is a key regulator of microvascular endothelial cell angiogenesis induced by VEGF and HGF secreted by KORS. Thus, GPC1 might constitute an interesting target to tackle alopecia in dermatology research.

Highlights

Forty to one hundred hairs are lost per day and constantly renewed
A high level of GPC1 gene expression was found in the keratinocytes of outer root sheath (KORS) and human hair follicle dermal papilla cells (HHFDPC) (Figures 1C,F)
This study suggests that GPC1 is involved in the human dermal microvascular endothelial cells (HDMEC) responses to growth factors secreted by KORS

Summary

Introduction

Forty to one hundred hairs are lost per day and constantly renewed. This renewal involves cyclic changes in the hair follicle (HF) (Myung and Ito, 2012; Sada and Tumbar, 2013). Each cycle is divided into three main stages: anagen, the growing phase of the hair; catagen, the HF size regression; and telogen, where the hair shaft remains anchored in the HF before being dislodged by the new growing hair. A HF can be divided into three parts. The isthmus extends from the end of the sebaceous duct to the bulb. It is made up of different concentric layers from the outside to the inside: the connective sheath, basal membrane, outer root sheath, inner

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