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Ultraviolet radiation attenuates thrombospondin 1 expression via PI3K-Akt activation in human keratinocytes

Cited 10 time in Web of Science Cited 11 time in Scopus
Authors
Kim, M. S.; Oh, Y. J.; Lee, S.; Kim, J. E.; Kim, K. H.; Chung, J. H.
Issue Date
2006-02-16
Publisher
Wiley-Blackwell
Citation
Photochem Photobiol. 2006 May-Jun;82(3):645-50.
Keywords
1-Phosphatidylinositol 3-Kinase/metabolismAngiogenic Proteins/genetics/radiation effectsDown-Regulation/genetics/radiation effectsHumansKeratinocytes/*metabolismProto-Oncogene Proteins c-akt/metabolismThrombospondin 1/*genetics/radiation effects*Ultraviolet Rays
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.
ISSN
0031-8655 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16478297

http://hdl.handle.net/10371/22576
DOI
https://doi.org/10.1562/2005-09-29-RA-702
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College of Medicine/School of Medicine (의과대학/대학원)Immunology (면역학전공)Journal Papers (저널논문_면역학전공)
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