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Basis for enhanced barrier function of pigmented skin.

Mao-Qiang Man1, Tzu-Kai Lin2, Juan L Santiago1

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Darker skin has a superior barrier function due to lower pH in the stratum corneum (SC), influenced by melanin. This study investigates how pigment affects epidermal barrier function in mice and humans.

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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.