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肌腱蛋白-C在特应性皮炎患者的皮肤病变中上调。

Tenascin-C is upregulated in the skin lesions of patients with atopic dermatitis.

作者信息

Ogawa Kaoru, Ito Mikito, Takeuchi Kaori, Nakada Akiko, Heishi Masayuki, Suto Hajime, Mitsuishi Kouichi, Sugita Yuji, Ogawa Hideoki, Ra Chisei

机构信息

Genox Research Inc., Ibaraki, Laboratory of Seeds Finding Technology, Eisai Co. Ltd., 5-1-3 Tokodai, Tsukuba-shi, Ibaraki 300-2635, Japan.

出版信息

J Dermatol Sci. 2005 Oct;40(1):35-41. doi: 10.1016/j.jdermsci.2005.06.001.

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.

摘要

背景

腱生蛋白-C是一种大型六聚体细胞外基质糖蛋白,在胚胎发育、肿瘤发生和伤口愈合过程中表达。在正常成人皮肤中,腱生蛋白-C的表达水平较低,但在皮肤肿瘤中表达水平升高,且在伤口愈合期间真皮层中的表达显著增加。虽然腱生蛋白-C的表达可被炎性细胞因子上调,但其在特应性皮炎(AD)中的作用仍不清楚。

目的

鉴定在AD中起作用的基因。

方法

我们使用DNA微阵列筛选AD患者皮损和非皮损皮肤中差异表达的基因。然后,我们用定量PCR监测人角质形成细胞或NC/Nga小鼠耳廓中与疾病相关的新基因的表达。

结果

我们发现,与患者的非皮损皮肤相比,腱生蛋白-C基因在皮损皮肤中的表达水平更高,而在银屑病患者或健康对照的皮肤中未上调。在人培养的角质形成细胞中,IL-4和IL-13可显著上调腱生蛋白-C的表达,IFN-γ可中度上调其表达。通过皮内注射螨抗原在NC/Nga小鼠耳部诱导的类AD皮肤病变中,腱生蛋白-C的表达也上调,且这种上调被泼尼松龙抑制。

结论

这些结果表明,腱生蛋白-C表达的上调是AD病变特有的,因此腱生蛋白-C可能在调节与AD病理相关的潜在炎症过程中起关键作用。

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