A meeting of two chronobiological systems: Circadian proteins period1 and bmal1 modulate the human hair cycle clock

Yusur Al-Nuaimi, Jonathan A. Hardman, Tamás Bíró, Iain S. Haslam, Michael P. Philpott, Balázs I. Tóth, Nilofer Farjo, Bessam Farjo, Gerold Baier, Rachel E B Watson, Benedetto Grimaldi, Jennifer E. Kloepper, Ralf Paus

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)610-619
Number of pages10
JournalJournal of Investigative Dermatology
Volume134
Issue number3
Early online date10 Oct 2013
DOIs
Publication statusPublished - Mar 2014
Externally publishedYes

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Al-Nuaimi, Y., Hardman, J. A., Bíró, T., Haslam, I. S., Philpott, M. P., Tóth, B. I., ... Paus, R. (2014). A meeting of two chronobiological systems: Circadian proteins period1 and bmal1 modulate the human hair cycle clock. Journal of Investigative Dermatology, 134(3), 610-619. https://doi.org/10.1038/jid.2013.366