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dc.contributor.authorNicu, C.
dc.contributor.authorO'Sullivan, J.D.B.
dc.contributor.authorRamos, R.
dc.contributor.authorTimperi, L.
dc.contributor.authorLai, T.
dc.contributor.authorFarjo, N.
dc.contributor.authorFarjo, B.
dc.contributor.authorPople, J.
dc.contributor.authorBhogal, R.
dc.contributor.authorHardman, J.A.
dc.contributor.authorPlikus, M.V.
dc.contributor.authorAnsell, David M.
dc.contributor.authorPaus, R.
dc.date.accessioned2021-02-15T10:46:24Z
dc.date.accessioned2021-02-16T13:25:29Z
dc.date.available2021-02-15T10:46:24Z
dc.date.available2021-02-16T13:25:29Z
dc.date.issued2021-07-01
dc.identifier.citationNicu C, O'Sullivan JDB, Ramos R et al (2021) Dermal adipose tissue secretes HGF to promote human hair growth and pigmentation. Journal of Investigative Dermatology. 141(7): 1633-1645. E13.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18343
dc.descriptionYesen_US
dc.description.abstractHair follicles (HFs) are immersed within dermal white adipose tissue (dWAT), yet human adipocyte-HF communication remains unexplored. Therefore, we investigated how perifollicular adipocytes affect the physiology of organ-cultured human anagen scalp HFs. Quantitative (immuno-)histomorphometry, microCT and transmission electron microscopy showed that the number and size of perifollicular adipocytes declined during anagen-catagen transition, whilst fluorescence lifetime imaging revealed increased lipid oxidation in adipocytes surrounding the bulge/sub-bulge region. Ex vivo, dWAT significantly stimulated hair matrix keratinocyte proliferation and HF pigmentation. Both dWAT pericytes and PREF1/DLK1+ adipocyte progenitors secreted hepatocyte growth factor (HGF) during human HF-dWAT co-culture, for which the c-Met receptor is expressed in the hair matrix and dermal papilla. These effects were abrogated by an HGF-neutralising antibody, and reproduced using recombinant HGF. Laser capture microdissection-based microarray analysis of the hair matrix showed that dWAT-derived HGF up-regulated KRT27, KRT73, KRT75, KRT84, KRT86 and TCHH. Mechanistically, HGF stimulated Wnt/β-catenin activity in the HM by inhibiting SFRP1 in the dermal papilla, up-regulating matrix AXIN2, LEF1, WNT6 and WNT10B expression. Our study demonstrates that dWAT regulates human hair growth and pigmentation via HGF secretion, and thus identifies important, molecular and cellular targets for therapeutic intervention in disorders of human hair growth and pigmentation.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.jid.2020.12.019en_US
dc.rights© 2021 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (https://creativecommons.org/licenses/by-nc-nd/4.0/)en_US
dc.subjectScatter factoren_US
dc.subjectFaten_US
dc.subjectSkinen_US
dc.subjectHirsutismen_US
dc.subjectAlopeciaen_US
dc.titleDermal adipose tissue secretes HGF to promote human hair growth and pigmentationen_US
dc.status.refereedYesen_US
dc.date.Accepted2020-12-03
dc.date.application2021-01-23
dc.typeArticleen_US
dc.date.EndofEmbargo2022-01-24
dc.type.versionAccepted manuscripten_US
dc.description.publicnotesThe full-text of this article will be released for public view at the end of the publisher embargo on 24 Jan 2022.en_US
dc.date.updated2021-02-15T10:46:28Z
refterms.dateFOA2021-02-16T13:27:04Z
dc.openaccess.statusGreenen_US


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