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KMID : 0984920100120010122
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Journal of Skin Barrier Research
2010 Volume.12 No. 1 p.122 ~ p.122
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A Decline of TRPV6 Function Derives from A Decrease of Vitamin D Activation and Accounts for Disturbed Epidermal Calcium Gradient Followed by Skin Barrier Alteration in Aged Skin
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Jung Min-Young
Lee Yoon-Hee
Yeh Byung-Il
Lee Seung-Hun
Choi Eung-Ho
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Abstract
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Epidermal Ca++ regulates keratinocyte differentiation and plays an important role in forming skin barrier. Because epidermal Ca++ gradient is restored with the recovery of skin barrier after its disruption, a disturbance in the recovery of Ca++ gradient delays skin barrier recovery. TRPV6 as a calcium ion channel, belonging to the superfamily of transient receptor potential channels constitutes an apical Ca++ entry mechanism in active Ca++ transport in the intestine, which has been also found in the epidermis of mammalian skin recently. TRPV6 modulates an influx of Ca++ into keratinocyte, and its expression is directly up-regulated by 1α, 25 dihydroxyvitamin D3. Facial skin of aged humans showed the loss of epidermal Ca++ gradient, and the synthesis of cutaneous vitamin D3 was declined with aging. We hypothesized that this disrupted epidermal Ca++ gradient is caused by a decrease of TRPV6 function due to decreased vitamin D activation with aging. The mRNA expression of TRPV6 and vitamin D receptor (VDR) on fully aged skin (87 weeks old hairless mice) decreased; moreover their mRNA expression was not enough increased after 3-day low-dose (50mJ/day) UVB irradiation compared to young skin. Western blot for TRPV6 and VDR protein expression showed very similar results with mRNA. Topical ketoconazole, an inhibitor of 1α, 25 dihydroxyvitamin D3, decreased TRPV6 expression even after UVB irradiation under immunohistochemical stain. In conclusion, a decline of TRPV6 function could be derived from decreased vitamin D activation and accounts for disturbed epidermal Ca++ gradient and altered skin barrier in aged skin.
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KEYWORD
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Calcium ion channel, TRPV6, Vitamin D receptor, Aged skin
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