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- 저자 : ( Peter M Eliasa ) (검색결과 1 건)
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New Hypotheses To Explain the Development and Subsequent Loss of Pigmentation in Humans
( Peter M Eliasa ),( Mary L Williamsc ) 한국피부장벽학회 2013 한국피부장벽학회지 Vol.15 No.2
Humans with darkly-pigmented skin (DS) (Fitzpatrick Type IV/V) display superior permeability barrier function and stratum corneum (SC) integrity/cohesion in comparison to humans with lightly-pigmented (Type I/II) skin (LS), independent of race, and barrier function is inferior in involved vs. uninvolved vitiligo skin. The reduced pH of the SC of DS skin (. ½ pH unit) could contribute to enhanced function, because reducing the pH of SC in LS individuals resets barrier function to DS levels. We evaluated here how pigmentation enhances epidermal barrier function in Skh1 (hairless albino) mice, which contain residual (non-melanized) melanocytes that lack pigment, and Skh2 (hairless pigmented) mice, where melanocytes generate abundant melanin restricted to the interfollicular epidermis. Barrier function was enhanced in Skh2 vs. Skh1 mice, which correlated with a more acidic pH that localized to the lower SC. The lower pH correlated further with persistence and extrusion of melanin granules into the extracellular spaces in the outer epidermis. Archived samples of DS human epidermis also showed melanin extrusion at and above the stratum granulosum (SG)-SC interface. Both acute barrier disruption and topical basic pH challenges accelerated melanin extrusion in Skh2, but not Skh1 mice, which correlated with a further decline in pH, enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, b-glucocerebrosidase and acidic sphingomyelinase, and accelerated maturation of SC extracellular lamellar bilayers. Yet, pigmented melanocytes also could enhance barrier function by paracrine mechanisms, because Skh2 epidermis displays enhanced mRNA and/or protein levels for: a) epidermal differentiation proteins; b) lipid synthetic proteins; c) lipid transporters; and d) lipid-processing enzymes, changes that likely cannot be attributed to reduced acidity alone. Together, these studies demonstrate that superior barrier function in pigmented epidermis can be attributed to both pH-lowering juxtacrine and as-yet-undefined paracrine mechanisms.
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