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

Nathan J. Hawkshaw, Jonathan A. Hardman, Iain Haslam, Asim Shahmalak, Amos Gilhar, Xinhong Lim, Ralf Paus

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.
Original languageEnglish
Article numbere2003705
Number of pages17
JournalPLoS Biology
Volume16
Issue number5
DOIs
Publication statusPublished - 8 May 2018

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hair follicles
cyclosporine
Hair Follicle
alopecia
Alopecia
Scalp
Hair
Cyclosporine
hairs
Skin
proteins
Catenins
Ligands
Hair-Specific Keratins
Hypertrichosis
Growth Disorders
Lead compounds
growth disorders
Microarray Analysis
Immunosuppressive Agents

Cite this

Hawkshaw, Nathan J. ; Hardman, Jonathan A. ; Haslam, Iain ; Shahmalak, Asim ; Gilhar, Amos ; Lim, Xinhong ; Paus, Ralf. / 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. In: PLoS Biology. 2018 ; Vol. 16, No. 5.
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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. / Hawkshaw, Nathan J.; Hardman, Jonathan A.; Haslam, Iain; Shahmalak, Asim; Gilhar, Amos; Lim, Xinhong; Paus, Ralf.

In: PLoS Biology, Vol. 16, No. 5, e2003705, 08.05.2018.

Research output: Contribution to journalArticle

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