Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-1alpha
The Korean Journal of Physiology and Pharmacology
;
: 91-97, 2010.
Article
Dans Anglais
| WPRIM
| ID: wpr-727336
ABSTRACT
Epidermal keratinocytes overgrow in response to ultraviolet-B (UVB), which may be associated with skin photoaging and cancer development. Recently, we found that HIF-1alpha controls the keratinocyte cell cycle and thereby contributes to epidermal homeostasis. A further study demonstrated that HIF-1alpha 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-1alpha in keratinocytes would prevent UVB-induced keratinocyte overgrowth. Among several agents known to induce HIF-1alpha, pyrithione-zinc (Py-Zn) overcame the UVB suppression of HIF-1alpha in cultured keratinocytes. Mechanistically, Py-Zn blocked the degradation of HIF-1alpha protein in keratinocytes, while it did not affect the synthesis of HIF-1alpha. 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-1alpha disappeared from nuclei of epidermal keratinocytes. However, a cream containing Py-Zn effectively prevented the skin thickening and up-regulated HIF-1alpha 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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Peau
/
Maladies de la peau
/
Tumeurs cutanées
/
Kératinocytes
/
Cycle cellulaire
/
Épiderme
/
Homéostasie
/
Hyperplasie
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
The Korean Journal of Physiology and Pharmacology
Année:
2010
Type:
Article
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