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Tenascin-C is upregulated in the skin lesions of patients with atopic dermatitis
Authors:Ogawa Kaoru  Ito Mikito  Takeuchi Kaori  Nakada Akiko  Heishi Masayuki  Suto Hajime  Mitsuishi Kouichi  Sugita Yuji  Ogawa Hideoki  Ra Chisei
Affiliation:Genox Research Inc., Ibaraki, Laboratory of Seeds Finding Technology, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba-shi, Ibaraki 300-2635, Japan. k6-ogawa@hhc.eisai.co.jp
Abstract:BACKGROUND: Tenascin-C is a large, hexameric extracellular matrix glycoprotein that is expressed during embryogenesis, carcinogenesis and wound healing. In normal adult human skin the expression level of tenascin-C is low, but levels are elevated in skin tumors and rise significantly in the dermal compartment during wound healing. Although the expression of tenascin-C could be upregulated by inflammatory cytokines, the role of tenascin-C in atopic dermatitis (AD) is still unclear. OBJECTIVE: To identify genes that plays a role in AD. METHODS: We screened for differentially expressed genes in lesional and non-lesional skin of AD patients using DNA microarray. Then we monitored with quantitative PCR the expression of the novel disease related genes in human keratinocytes or pinnae from NC/Nga mice. RESULTS: We found that tenascin-C gene expression was expressed at higher levels in lesional skin compared to non-lesional skin of the patients, whereas it was not upregulated in the skin of psoriatic patients or healthy controls. In human cultured keratinocytes, tenascin-C was markedly upregulated by IL-4 and IL-13, and moderately upregulated by IFN-gamma. Tenascin-C expression was also upregulated in the AD-like skin lesions induced in NC/Nga mice ears by intradermal injection of mite antigen, and this upregulation was inhibited by prednisolone. CONCLUSION: These results suggest that upregulation of the tenascin-C expression is specific to AD lesions, and that tenascin-C may therefore play a critical role in regulating the underlining inflammatory processes, which are involved in the pathology of AD.
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