Please use this identifier to cite or link to this item:
https://doi.org/10.1371/journal.pbio.2003705
DC Field | Value | |
---|---|---|
dc.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 | |
dc.contributor.author | Hawkshaw N.J. | |
dc.contributor.author | Hardman J.A. | |
dc.contributor.author | Haslam I.S. | |
dc.contributor.author | Shahmalak A. | |
dc.contributor.author | Gilhar A. | |
dc.contributor.author | Lim X. | |
dc.contributor.author | Paus R. | |
dc.date.accessioned | 2019-11-08T06:42:17Z | |
dc.date.available | 2019-11-08T06:42:17Z | |
dc.date.issued | 2018 | |
dc.identifier.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 | |
dc.identifier.issn | 15449173 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/161883 | |
dc.description.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/ | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20191101 | |
dc.subject | beta catenin | |
dc.subject | cyclosporine | |
dc.subject | dermatological agent | |
dc.subject | growth promotor | |
dc.subject | keratin | |
dc.subject | ligand | |
dc.subject | secreted frizzled related protein 1 | |
dc.subject | unclassified drug | |
dc.subject | way 316606 | |
dc.subject | Wnt protein | |
dc.subject | cyclosporine | |
dc.subject | membrane protein | |
dc.subject | SFRP1 protein, human | |
dc.subject | signal peptide | |
dc.subject | Article | |
dc.subject | bioassay | |
dc.subject | concentration (parameters) | |
dc.subject | confounding variable | |
dc.subject | controlled study | |
dc.subject | down regulation | |
dc.subject | ex vivo study | |
dc.subject | hair follicle | |
dc.subject | hair growth | |
dc.subject | hair loss | |
dc.subject | hair root | |
dc.subject | human | |
dc.subject | human tissue | |
dc.subject | immunofluorescence microscopy | |
dc.subject | in situ hybridization | |
dc.subject | male | |
dc.subject | microarray analysis | |
dc.subject | papillary dermis | |
dc.subject | pharmacological assay | |
dc.subject | protein expression | |
dc.subject | protein function | |
dc.subject | protein targeting | |
dc.subject | quantitative analysis | |
dc.subject | reverse transcription polymerase chain reaction | |
dc.subject | Wnt signaling | |
dc.subject | alopecia | |
dc.subject | antagonists and inhibitors | |
dc.subject | drug effect | |
dc.subject | hair follicle | |
dc.subject | organ culture technique | |
dc.subject | preclinical study | |
dc.subject | Alopecia | |
dc.subject | Cyclosporine | |
dc.subject | Drug Evaluation, Preclinical | |
dc.subject | Hair Follicle | |
dc.subject | Humans | |
dc.subject | Intercellular Signaling Peptides and Proteins | |
dc.subject | Male | |
dc.subject | Membrane Proteins | |
dc.subject | Organ Culture Techniques | |
dc.subject | Wnt Signaling Pathway | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1371/journal.pbio.2003705 | |
dc.description.sourcetitle | PLoS Biology | |
dc.description.volume | 16 | |
dc.description.issue | 5 | |
dc.description.page | e2003705 | |
Appears in Collections: | Elements Staff Publications |
Show simple item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1371_journal_pbio_2003705.pdf | 12.78 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License