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Alkaline ceramidase 1 is essential for mammalian skin homeostasis and regulating whole-body energy expenditure.
Authors
David J Adams
Mark J Arends
+18 more
Thomas Brenn
Antonella Galli
Diane Gleeson
Leanne Glover
Angela Green
Camilla Ingvorsen
Natasha A Karp
David Lafont
Christopher J Lelliott
Kifayathullah Liakath-Ali
Hayley J Protheroe
Ed Ryder
Anneliese O Speak
Sarah Spiegel
Louise van der Weyden
Valerie E Vancollie
Gema Vizcay-Barrena
Fiona M Watt
Publication date
30 May 2016
Publisher
J Pathol
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on
PubMed
Abstract
The epidermis is the outermost layer of skin that acts as a barrier to protect the body from the external environment and to control water and heat loss. This barrier function is established through the multistage differentiation of keratinocytes and the presence of bioactive sphingolipids such as ceramides, the levels of which are tightly regulated by a balance of ceramide synthase and ceramidase activities. Here we reveal the essential role of alkaline ceramidase 1 (Acer1) in the skin. Acer1-deficient (Acer1(-/-) ) mice showed elevated levels of ceramide in the skin, aberrant hair shaft cuticle formation and cyclic alopecia. We demonstrate that Acer1 is specifically expressed in differentiated interfollicular epidermis, infundibulum and sebaceous glands and consequently Acer1(-/-) mice have significant alterations in infundibulum and sebaceous gland architecture. Acer1(-/-) skin also shows perturbed hair follicle stem cell compartments. These alterations result in Acer1(-/-) mice showing increased transepidermal water loss and a hypermetabolism phenotype with associated reduction of fat content with age. We conclude that Acer1 is indispensable for mammalian skin homeostasis and whole-body energy homeostasis. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland
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info:doi/10.1002%2Fpath.4737
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