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1 May 2006 Ultraviolet Radiation Attenuates Thrombospondin 1 Expression via PI3K-Akt Activation in Human Keratinocytes
Mi-Sun Kim, Youn Jin Oh, SeRah Lee, Ji Eun Kim, Kyu Han Kim, Jin Ho Chung
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Abstract

Thrombospondin 1 (TSP1) is an extracellular glycoprotein and a recognized inhibitor of angiogenesis. Recent studies have demonstrated that UV radiation induces an angiogenic switch, by which it alters the balance between pro- and anti-angiogenic factors in the skin. Here we describe the effects of acute UV exposure on TSP1 expression in human skin epidermis, primary keratinocytes and the epidermal cell line HaCaT. We found that protein and mRNA expressions of TSP1 are significantly reduced in human skin in vivo and in keratinocytes in vitro by a single UV exposure. In human skin and keratinocytes, UV exposure induced the phosphorylation of Akt, a downstream target of the PI3K pathways. Specific inhibitors of PI3K, wortmannin and LY294002, completely blocked Akt activation and UV-induced TSP1 downregulation in keratinocytes. We showed that a specific Akt phosphorylation inhibitor and small interfering RNA–mediated Akt depletion were also blocked by UV-induced TSP1 downregulation in keratinocytes. In conclusion, our findings demonstrate that acute UV exposure downregulates TSP1 expression via PI3K-Akt activation in human keratinocytes. These novel findings may help us understand the regulatory mechanisms of UV-induced skin angiogenesis.

Mi-Sun Kim, Youn Jin Oh, SeRah Lee, Ji Eun Kim, Kyu Han Kim, and Jin Ho Chung "Ultraviolet Radiation Attenuates Thrombospondin 1 Expression via PI3K-Akt Activation in Human Keratinocytes," Photochemistry and Photobiology 82(3), 645-650, (1 May 2006). https://doi.org/10.1562/2005-09-29-RA-702
Received: 29 September 2005; Accepted: 1 February 2006; Published: 1 May 2006
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