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PLoS Biol. 2018 May 8;16(5):e2003705. doi: 10.1371/journal.pbio.2003705. eCollection 2018 May.

Identifying novel strategies for treating human hair loss disorders: Cyclosporine A suppresses the Wnt inhibitor, SFRP1, in the dermal papilla of human scalp hair follicles.

Author information

1
Centre for Dermatology Research, University of Manchester, Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Centre, Manchester, United Kingdom.
2
Department of Biological Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom.
3
Crown Clinic, Manchester, United Kingdom.
4
Skin Research Laboratory, Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
5
Institute of Medical Biology, Agency for Science, Technology, and Research, Singapore.
6
Skin Research Institute of Singapore, Singapore.
7
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
8
Duke-NUS Medical School, Singapore.
9
Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America.

Abstract

Hair growth disorders often carry a major psychological burden. Therefore, more effective human hair growth-modulatory agents urgently need to be developed. Here, we used the hypertrichosis-inducing immunosuppressant, Cyclosporine A (CsA), as a lead compound to identify new hair growth-promoting molecular targets. Through microarray analysis we identified the Wnt inhibitor, secreted frizzled related protein 1 (SFRP1), as being down-regulated in the dermal papilla (DP) of CsA-treated human scalp hair follicles (HFs) ex vivo. Therefore, we further investigated the function of SFRP1 using a pharmacological approach and found that SFRP1 regulates intrafollicular canonical Wnt/β-catenin activity through inhibition of Wnt ligands in the human hair bulb. Conversely, inhibiting SFRP1 activity through the SFRP1 antagonist, WAY-316606, enhanced hair shaft production, hair shaft keratin expression, and inhibited spontaneous HF regression (catagen) ex vivo. Collectively, these data (a) identify Wnt signalling as a novel, non-immune-inhibitory CsA target; (b) introduce SFRP1 as a physiologically important regulator of canonical β-catenin activity in a human (mini-)organ; and (c) demonstrate WAY-316606 to be a promising new promoter of human hair growth. Since inhibiting SFRP1 only facilitates Wnt signalling through ligands that are already present, this 'ligand-limited' therapeutic strategy for promoting human hair growth may circumvent potential oncological risks associated with chronic Wnt over-activation.

PMID:
29738529
PMCID:
PMC5940179
DOI:
10.1371/journal.pbio.2003705
[Indexed for MEDLINE]
Free PMC Article

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