Basis for enhanced barrier function of pigmented skin.

Area of Science:

• Skin Biology
• Epidermal Barrier Function
• Melanin Physiology

Background:

• Darkly pigmented skin exhibits enhanced permeability barrier function compared to lightly pigmented skin.
• Reduced stratum corneum (SC) pH in darker skin is a potential mechanism for its superior barrier function.
• Acidification of lightly pigmented SC can restore barrier function to levels seen in darker skin.

Purpose of the Study:

• To investigate the influence of pigment-dependent pH reduction on epidermal barrier function.
• To compare barrier function and pH regulation between pigmented and non-pigmented hairless mouse models (SKH2/J vs. SKH1).
• To elucidate the role of melanin extrusion and specific enzymes in maintaining epidermal barrier homeostasis.

Main Methods:

• Comparative analysis of epidermal barrier function and SC pH in pigmented (SKH2/J) and non-pigmented (SKH1) hairless mice.
• Assessment of SC reacidification following barrier disruption and pH challenges.
• Evaluation of secretory phospholipase A2f (sPLA2f) expression.
• Analysis of ceramide-generating enzyme activity (β-glucocerebrosidase, acidic sphingomyelinase).
• Organotypic culture of human keratinocytes with varying pigmentation.

Main Results:

• Pigmented SKH2/J mice demonstrated enhanced permeability barrier homeostasis compared to non-pigmented SKH1 mice, correlating with lower SC pH and melanin granule extrusion.
• Both mouse models showed accelerated SC reacidification and induced melanin extrusion upon barrier disruption or basic pH challenge, but SKH2/J mice responded more effectively.
• SKH2/J mice exhibited enhanced expression of sPLA2f, an SC acidifying enzyme.
• Enhanced barrier function in SKH2/J mice was linked to increased activity of pH-dependent enzymes, promoting ceramide generation and SC lamellar bilayer maturation.
• Darkly pigmented human keratinocyte cultures showed superior barrier function compared to lightly pigmented cultures.

Conclusions:

• The superior barrier function of pigmented epidermis is significantly attributed to the pH-lowering effect of melanin persistence and extrusion.
• Enhanced sPLA2f expression in pigmented skin contributes to improved barrier function.
• Melanin's interaction with SC pH is a key factor in regulating epidermal barrier homeostasis and maturation.