Pharmacological stimulation of Edar signaling in the adult enhances sebaceous gland size and function
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Impaired ectodysplasin A (EDA) receptor (EDAR) signaling affects ectodermally derived structures including teeth, hair follicles, and cutaneous glands. The X-linked hypohidrotic ectodermal dysplasia (XLHED), resulting from EDA deficiency, can be rescued with lifelong benefits in animal models by stimulation of ectodermal appendage development with EDAR agonists. Treatments initiated later in the developmental period restore progressively fewer of the affected structures. It is unknown whether EDAR stimulation in adults with XLHED might have beneficial effects. In adult Eda mutant mice treated for several weeks with agonist anti-EDAR antibodies, we find that sebaceous gland size and function can be restored to wild-type levels. This effect is maintained upon chronic treatment but reverses slowly upon cessation of treatment. Sebaceous glands in all skin regions respond to treatment, although to varying degrees, and this is accompanied in both Eda mutant and wild-type mice by sebum secretion to levels higher than those observed in untreated controls. Edar is expressed at the periphery of the glands, suggesting a direct homeostatic effect of Edar stimulation on the sebaceous gland. Sebaceous gland size and sebum production may serve as biomarkers for EDAR stimulation, and EDAR agonists may improve skin dryness and eczema frequently observed in XLHED.
Kowalczyk-Quintas , C , Schuepbach-Mallepell , S , Willen , L , Smith , T K , Huttner , K , Kirby , N , Headon , D J & Schneider , P 2015 , ' Pharmacological stimulation of Edar signaling in the adult enhances sebaceous gland size and function ' Journal of Investigative Dermatology , vol 135 , no. 2 , pp. 359-368 . DOI: 10.1038/jid.2014.382
Journal of Investigative Dermatology
© 2015, The Society for Investigative Dermatology. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at www.sciencedirect.com / https://dx.doi.org/10.1038/jid.2014.382
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