S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-1 alpha
- Cho, Young-Suk; Lee, Kyung-Hoon; Park, Jong-Wan
- Issue Date
- KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY; Vol.14 2; 91-97
- 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 alpha controls the keratinocyte cell cycle and thereby contributes to epidermal homeostasis. A further study demonstrated that HIF-1 alpha 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 alpha in keratinocytes would prevent UVB-induced keratinocyte overgrowth. Among several agents known to induce HIF-1 alpha, pyrithione-zinc (Py-Zn) overcame the UVB suppression of HIF-1 alpha in cultured keratinocytes. Mechanistically, Py-Zn blocked the degradation of HIF-1 alpha protein in keratinocytes, while it did not affect the synthesis of HIF-1 alpha. 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 alpha disappeared from nuclei of epidermal keratinocytes. However, a cream containing Py-Zn effectively prevented the skin thickening and up-regulated HIF-1 alpha 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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