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KMID : 0811720100140020091
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Korean Journal of Physiology & Pharmacology
2010 Volume.14 No. 2 p.91 ~ p.97
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Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-1?
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Cho Young-Suk
Lee Kyung-Hoon
Park Jong-Wan
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Abstract
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Epidermal keratinocytes overgrow in response to ultraviolet-B (UVB), which may be associated with skin photoaging and cancer development. Recently, we found that HIF-1? controls the keratinocyte cell cycle and thereby contributes to epidermal homeostasis. A further study demonstrated that HIF-1? is down-regulated by UVB and that this process is involved in UVB-induced skin hyperplasia. Therefore, we hypothesized that the forced expression of HIF-1? in keratinocytes would prevent UVB-induced keratinocyte overgrowth. Among several agents known to induce HIF-1?, pyrithione-zinc (Py-Zn) overcame the UVB suppression of HIF-1? in cultured keratinocytes. Mechanistically, Py-Zn blocked the degradation of HIF-1? protein in keratinocytes, while it did not affect the synthesis of HIF-1?. Moreover, the p21 cell cycle inhibitor was down-regulated after UVB exposure, but was robustly induced by Py-Zn. In mice repeatedly irradiated with UVB, the epidermis became hyperplastic and HIF-1? disappeared from nuclei of epidermal keratinocytes. However, a cream containing Py-Zn effectively prevented the skin thickening and up-regulated HIF-1? to the normal level. These results suggest that Py-Zn is a potential agent to prevent UVB-induced photoaging and skin cancer development. This work also provides insight into a molecular target for treatment of UVB-induced skin diseases.
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KEYWORD
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Ultraviolet, Skin, Hyperplasia, Hypoxia-inducible factor-1?, Pyrithione-zinc
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