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    Dermal adipose tissue secretes HGF to promote human hair growth and pigmentation

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    Publication date
    2021
    End of Embargo
    2022-01-24
    Author
    Nicu, C.
    O'Sullivan, J.D.B.
    Ramos, R.
    Timperi, L.
    Lai, T.
    Farjo, N.
    Farjo, B.
    Pople, J.
    Bhogal, R.
    Hardman, J.A.
    Plikus, M.V.
    Ansell, David M.
    Paus, R.
    Show allShow less
    Keyword
    Scatter factor
    Fat
    Skin
    Hirsutism
    Alopecia
    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/)
    Peer-Reviewed
    Yes
    Open Access status
    Green
    
    Metadata
    Show full item record
    Abstract
    Hair 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.
    URI
    http://hdl.handle.net/10454/18343
    Version
    Accepted manuscript
    Citation
    Nicu 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. Accepted for publication.
    Link to publisher’s version
    https://doi.org/10.1016/j.jid.2020.12.019
    Type
    Article
    Notes
    The full-text of this article will be released for public view at the end of the publisher embargo on 24 Jan 2022.
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    Life Sciences Publications

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