UVB induces a biphasic response of HIF-1α in cultured human keratinocytes

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15 Citations (Scopus)

Abstract

Hypoxia in the skin is important in chronic degenerative dermo-epidermal changes, inflammation, photoageing and carcinogenesis. In these processes, vascular endothelial growth factor (VEGF) plays a crucial role and is known to be affected by ultraviolet radiation (UVR). Hypoxia-inducible factor-1 (HIF-1) closely regulates the expression of VEGF in several experimental settings. We set out to study the impact of acute UVB irradiation on the level of HIF-1 as a major regulator of hypoxia-induced genes. Effects of UVB exposure on HIF-1α expression were investigated in HaCaT cells after a single irradiation by Western blots. Downstream target gene expression was measured by quantitative real-time polymerace chair reaction (PCR). UVB treatment resulted in an initial decrease of the HIF-1α protein level followed by a subsequent prolonged increase. If cells were exposed to additional UVB irradiation, another decrease in HIF-1α was provoked, similar to the original effect. The observed changes followed a strict timeline and were dose-dependent. The role of the PI3K/AKT pathway was examined. No change in the total level of AKT after UVB treatment was seen; however, its phosphorylation level was found to be markedly higher. In accordance with these observations, wortmannin, an inhibitor of PI3-kinase effectively blocked the UVB-induced increase in HIF-1α. In agreement with previous findings, UVB irradiation increased VEGF and haem oxygenase-1 mRNA levels determined by quantitative real-time PCR. It is concluded that changes in HIF-1α expression underlie the alterations in expression of VEGF upon UVB irradiation. Our findings indicate the involvement of PI3K in UVB-mediated HIF-1α upregulation.

Original languageEnglish
Pages (from-to)335-342
Number of pages8
JournalExperimental Dermatology
Volume17
Issue number4
DOIs
Publication statusPublished - Apr 1 2008

Keywords

  • AKT
  • HIF-1
  • HaCaT
  • Keratinocyte
  • P13K
  • UVB

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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