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Published on: September 7, 2013
The expression and activation of protease-activated receptor-2 correlate with skin color
Laura Babiarz-Magee1, Nannan Chen, Miri Seiberg
1Johnson and Johnson Skin Research Center, CPPW, Skillman, NJ 08558, USA.
Abstract:
Skin color results from the production and distribution of melanin in the epidermis. The protease-activated receptor-2 (PAR-2), expressed on keratinocytes but not on melanocytes, is involved in melanosome uptake via phagocytosis, and modulation of PAR-2 activation affects skin color. The pattern of melanosome distribution within the epidermis is skin color-dependent. In vitro, this distribution pattern is regulated by the ethnic origin of the keratinocytes, not the melanocytes. Therefore, we hypothesized that PAR-2 may play a role in the modulation of pigmentation in a skin type-dependent manner. We examined the expression of PAR-2 and its activator, trypsin, in human skins with different pigmentary levels. Here we show that PAR-2 and trypsin are expressed in higher levels, and are differentially localized in highly pigmented, relative to lightly pigmented skins. Moreover, highly pigmented skins exhibit an increase in PAR-2-specific protease cleavage ability. Microsphere phagocytosis was more efficient in keratinocytes from highly pigmented skins, and PAR-2 induced phagocytosis resulted in more efficient microsphere ingestion and more compacted microsphere organization in dark skin-derived keratinocytes. These results demonstrate that PAR-2 expression and activity correlate with skin color, suggesting the involvement of PAR-2 in ethnic skin color phenotypes.
Insights
Protease-activated receptor-2 (PAR-2) plays a key role in skin pigmentation. Higher PAR-2 expression and activity in darker skin types suggest its involvement in ethnic skin color differences.
Area of Science:
- Dermatology
- Cell Biology
- Biochemistry
Background:
- Skin color is determined by melanin production and distribution.
- Protease-activated receptor-2 (PAR-2), found on keratinocytes, influences melanosome uptake and affects skin color.
- Melanosome distribution patterns are dependent on skin color and keratinocyte origin.
Purpose of the Study:
- To investigate the role of PAR-2 in skin pigmentation modulation in a skin type-dependent manner.
- To examine the expression and activity of PAR-2 and its activator, trypsin, in human skin with varying pigmentation levels.
Main Methods:
- Comparative analysis of PAR-2 and trypsin expression and localization in lightly versus highly pigmented human skin.
- Assessment of PAR-2-specific protease cleavage ability in different skin types.
- In vitro phagocytosis assays using microspheres in keratinocytes derived from various skin pigmentation backgrounds.
Main Results:
- PAR-2 and trypsin expression levels and localization differed significantly between highly pigmented and lightly pigmented skin.
- Highly pigmented skin exhibited enhanced PAR-2-specific protease cleavage ability.
- Keratinocytes from highly pigmented skin showed more efficient microsphere phagocytosis, particularly when induced by PAR-2.
Conclusions:
- PAR-2 expression and activity correlate with skin color.
- The findings suggest a significant involvement of PAR-2 in the determination of ethnic skin color phenotypes.
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