Localisation and regulation of cholesterol transporters in the human hair follicle: mapping changes across the hair cycle

Megan A Palmer,Eleanor Smart,Iain S Haslam

doi:10.1007/s00418-020-01957-8

Abstract

Cholesterol has long been suspected of influencing hair biology, with dysregulated homeostasis implicated in several disorders of hair growth and cycling. Cholesterol transport proteins play a vital role in the control of cellular cholesterol levels and compartmentalisation. This research aimed to determine the cellular localisation, transport capability and regulatory control of cholesterol transport proteins across the hair cycle. Immunofluorescence microscopy in human hair follicle sections revealed differential expression of ATP-binding cassette (ABC) transporters across the hair cycle. Cholesterol transporter expression (ABCA1, ABCG1, ABCA5 and SCARB1) reduced as hair follicles transitioned from growth to regression. Staining for free cholesterol (filipin) revealed prominent cholesterol striations within the basement membrane of the hair bulb. Liver X receptor agonism demonstrated active regulation of ABCA1 and ABCG1, but not ABCA5 or SCARB1 in human hair follicles and primary keratinocytes. These results demonstrate the capacity of human hair follicles for cholesterol transport and trafficking. Future studies examining the role of cholesterol transport across the hair cycle may shed light on the role of lipid homeostasis in human hair disorders.

Highlights

Cholesterol plays a vital role in cutaneous physiology, being integral to epidermal barrier function (Feingold 2009; Wertz 2000) and acting as a metabolic precursor in steroid hormone synthesis (Payne and Hales 2004; Slominski et al 2013; Thiboutot et al 2003)
We describe the expression, localisation and regulation of transport proteins involved in cholesterol homeostasis across the human hair cycle
ABCA1 and ABCG1, two highly characterised proteins involved in modulating intracellular cholesterol levels, displayed both membranous and intracellular staining patterns as previously described (Neufeld et al 2001)

Summary

Introduction

Cholesterol plays a vital role in cutaneous physiology, being integral to epidermal barrier function (Feingold 2009; Wertz 2000) and acting as a metabolic precursor in steroid hormone synthesis (Payne and Hales 2004; Slominski et al 2013; Thiboutot et al 2003). Cholesterol modifications are vital for signal transduction in the Wnt-β-catenin and hedgehog pathways (Incardona and Eaton 2000), both of which are fundamental in the control of human hair follicle (HF) cycling (Lee and Tumbar 2012)

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