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https://doi.org/10.1371/journal.pbio.2003705
Title: | 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 | Authors: | Hawkshaw N.J. Hardman J.A. Haslam I.S. Shahmalak A. Gilhar A. Lim X. Paus R. |
Keywords: | beta catenin cyclosporine dermatological agent growth promotor keratin ligand secreted frizzled related protein 1 unclassified drug way 316606 Wnt protein cyclosporine membrane protein SFRP1 protein, human signal peptide Article bioassay concentration (parameters) confounding variable controlled study down regulation ex vivo study hair follicle hair growth hair loss hair root human human tissue immunofluorescence microscopy in situ hybridization male microarray analysis papillary dermis pharmacological assay protein expression protein function protein targeting quantitative analysis reverse transcription polymerase chain reaction Wnt signaling alopecia antagonists and inhibitors drug effect hair follicle organ culture technique preclinical study Alopecia Cyclosporine Drug Evaluation, Preclinical Hair Follicle Humans Intercellular Signaling Peptides and Proteins Male Membrane Proteins Organ Culture Techniques Wnt Signaling Pathway |
Issue Date: | 2018 | Citation: | Hawkshaw N.J., Hardman J.A., Haslam I.S., Shahmalak A., Gilhar A., Lim X., Paus R. (2018). 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. PLoS Biology 16 (5) : e2003705. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pbio.2003705 | Rights: | Attribution 4.0 International | 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/?-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 ?-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. ? 2018 Hawkshaw et al. http://creativecommons.org/licenses/by/4.0/ | Source Title: | PLoS Biology | URI: | https://scholarbank.nus.edu.sg/handle/10635/161883 | ISSN: | 15449173 | DOI: | 10.1371/journal.pbio.2003705 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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