Basis for enhanced barrier function of pigmented skin
Man, Mao-Qiang (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Lin, Tzu-Kai (Graduate Institute of Clinical Medicine, National Cheng Kung University Medical College & Department of Dermatology, Tainan, Taiwan)
Santiago, Juan Luis (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Celli, Anna (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Zhong, Lily (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Huang, Zhi-Ming (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Roelandt, Truus (Department of Dermatology, Universitair Ziekenhuis Brussel, Brussels, Belgium)
Hupe, Melanie (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Sundberg, John P. (Department of Research and Development, The Jackson Laboratory, Bar Harbor, ME)
Silva, Kathleen A. (Department of Research and Development, The Jackson Laboratory, Bar Harbor, ME)
Crumrine, Debra (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Martin-Ezquerra, Gemma (Institut Hospital del Mar d'Investigacions Mèdiques)
Trullas, Carles (ISDIN, Research & Development, Barcelona, Spain)
Sun, Richard (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Wakefield, Joan S. (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Wei, Maria L. (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Feingold, Kenneth R. (Medical Service, Department of Veterans Affairs Medical Center, and Department of Metabolism, UCSF, San Francisco, CA)
Mauro, Theodora M. (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Elias, Peter M.. (Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, CA)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2014
Abstract:	Humans with darkly-pigmented skin display superior permeability barrier function in comparison to humans with lightly-pigmented skin. The reduced pH of the stratum corneum (SC) of darkly-pigmented skin could account for enhanced function, because acidifying lightly-pigmented human SC resets barrier function to darkly-pigmented levels. In SKH1 (non-pigmented) vs. SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J vs. SKH1 mice, correlating with a reduced pH in the lower SC that co-localizes with the extrusion of melanin granules. Darkly-pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate re-acidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly-pigmented-bearing human keratinocytes display enhanced barrier function in comparison to lightly-pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression.
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Barrier function ; Melanin ; Melanocytes ; Melanosomes ; Ph ; Pigmentation ; Crl:SKH1 ; SKH2/J hairless mice
Published in:	The Journal of investigative dermatology, Vol. 134 (april 2014) , p. 2399-2407, ISSN 1523-1747

DOI: 10.1038/jid.2014.187
PMID: 24732399

20 p, 1.3 MB

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