A meeting of two chronobiological systems: circadian proteins Period1 and BMAL1 modulate the human hair cycle clock

J Invest Dermatol. 2014 Mar;134(3):610-619. doi: 10.1038/jid.2013.366.

Yusur Al-Nuaimi ¹, Jonathan A Hardman ², Tamás Bíró ³, Iain S Haslam ¹, Michael P Philpott ⁴, Balázs I Tóth ³, Nilofer Farjo ⁵, Bessam Farjo ⁵, Gerold Baier ⁶, Rachel E B Watson ¹, Benedetto Grimaldi ⁷, Jennifer E Kloepper ⁸, Ralf Paus ⁹

Affiliations

1 The Dermatology Centre, Salford Royal NHS Foundation Trust and the Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
2 The Dermatology Centre, Salford Royal NHS Foundation Trust and the Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK; Doctoral Training Centre in Integrative Systems Biology, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK.
3 DE-MTA ''Lendulet'' Cell Physiology Group, Department of Physiology, University of Debrecen, Debrecen, Hungary.
4 Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
5 Farjo Medical Centre, Manchester, UK.
6 Faculty of Life Sciences, Division of Biosciences, Department of Cell and Developmental Biology, University College London, London, UK.
7 Italian Institute of Technology, Genova, Italy.
8 Department of Dermatology, University of Luebeck, Luebeck, Germany.
9 The Dermatology Centre, Salford Royal NHS Foundation Trust and the Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK; Department of Dermatology, University of Luebeck, Luebeck, Germany. Electronic address: ralf.paus@uksh.de.

PMID: 24005054 DOI: 10.1038/jid.2013.366

Abstract

The hair follicle (HF) is a continuously remodeled mini organ that cycles between growth (anagen), regression (catagen), and relative quiescence (telogen). As the anagen-to-catagen transformation of microdissected human scalp HFs can be observed in organ culture, it permits the study of the unknown controls of autonomous, rhythmic tissue remodeling of the HF, which intersects developmental, chronobiological, and growth-regulatory mechanisms. The hypothesis that the peripheral clock system is involved in hair cycle control, i.e., the anagen-to-catagen transformation, was tested. Here we show that in the absence of central clock influences, isolated, organ-cultured human HFs show circadian changes in the gene and protein expression of core clock genes (CLOCK, BMAL1, and Period1) and clock-controlled genes (c-Myc, NR1D1, and CDKN1A), with Period1 expression being hair cycle dependent. Knockdown of either BMAL1 or Period1 in human anagen HFs significantly prolonged anagen. This provides evidence that peripheral core clock genes modulate human HF cycling and are an integral component of the human hair cycle clock. Specifically, our study identifies BMAL1 and Period1 as potential therapeutic targets for modulating human hair growth.

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