Ultraviolet radiation attenuates thrombospondin 1 expression via PI3K-Akt activation in human keratinocytes.
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.
Department of Dermatology, Seoul National University College of Medicine, Institute of Dermatological Science, Medical Research, Korea.
Mi-Sun
MS
Kim
Youn Jin
YJ
Oh
Serah
S
Lee
Ji Eun
JE
Kim
Kyu Han
KH
Kim
Jin Ho
JH
Chung
D042501:Angiogenic Proteins / Q000235:genetics / Q000528:radiation effects; D015536:Down-Regulation / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
D042501:Angiogenic Proteins; D019700:Thrombospondin 1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt