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Ultravlolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K/AKT/DEC1 pathway

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Abstract

The aim of this research was to explore the effects and signaling pathway of ultraviolet-B (UVB) irradiation on the expression of hypoxia-inducible factor 1α (HIF-1α) and transferrin receptor (TfR). HIF-1α protein was measured by Western blot method. Expressions of epidermal growth factor receptor (EGFR), phosphor-EGF-R and TfR after UVB irradiation were determined with flow cytometry. After UVB irradiation, mRNA levels of HIF-1α and TfR were detected by real time-PCR. Results showed that compared with control groups, UVB was able to induce HIF1α and TfR protein expression in a dose-and time-dependent manner in HaCat cells (P < 0.05). TfR mRNA was expressed in a dose-dependent manner and reached a peak at the 8th hour in HaCat cells (P < 0.05) whereas HIF-1α mRNA expression was not affected by UVB treatment (P>0.05). The EGFR/PI3K/AKT signaling pathway was required for the induction of HIF-1α and TfR expression induced by UVB. UVB induced activation of EGFR in HaCat cells and EGFR regulated expression of TfR and HIF-1α. EGFR (−/−) MEF did not increase the HIF1 expression following UVB irradiation (P>0.05). In contrast, EGFR (+/+) MEF strongly enhanced HIF1α expression after UVB irradiation (P < 0.05). PD153035, a selective inhibitor of EGFR tyrosine kinase, inhibited the TfR protein expression in UVB-treated cells in a dose-dependent manner (P < 0.05). PI3K inhibitors, LY294002 and wortmannin, inhibited HIF-1α and TfR expressions induced by UVB (P < 0.05). The DEC1 (−/−) HaCat cells did not increase their TfR and HIF-1α expressions following UVB irradiation (P>0.05). In contrast, DEC1 (+/+) HaCat cells strongly enhanced TfR and HIF-1α protein expression after UVB irradiation (P < 0.05). We conclude that UVB induces TfR and HIF-1α expressions via EGFR/PI3K/AKT/DEC1 signaling pathway.

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  1. Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Li Yanhua MD & Bi Zhigang MD

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Li, Y., Bi, Z. Ultravlolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K/AKT/DEC1 pathway. Front. Med. China 1, 79–86 (2007). https://doi.org/10.1007/s11684-007-0016-4

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