Claudin reduction may relate to an impaired skin barrier in rosacea
Claudin reduction may relate to an impaired skin barrier in rosacea
复制标题
密蛋白减少可能与红斑痤疮皮肤屏障受损有关。
DOI：
10.1111/1346-8138.14792
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发表时间：
2019-04-01
影响因子：
3.1
通讯作者：
Li, Ji
中科院分区：
文献类型：
--
作者：
Deng, Zhili;Chen, Mengting;Li, Ji
酒渣鼻是一种慢性炎症性皮肤病，其病理生理机制在很大程度上仍不明确。尽管近期研究表明皮肤对化学、热和生物刺激具有超敏性，但没有直接的分子证据表明酒渣鼻患者的皮肤屏障受损。在本研究中，我们证实大多数紧密连接蛋白（CLDN）的mRNA水平在酒渣鼻患者的皮损处降低，尤其是红斑毛细血管扩张型（ETR）和丘疹脓疱型（PPR）亚型，紧密连接蛋白是决定上皮细胞间细胞旁通路主要屏障的紧密连接的主要成分。免疫组化分析显示ETR和PPR患者表皮中CLDN1、CLDN3、CLDN4和CLDN5的表达显著降低。然而，其他皮肤屏障基因，如丝聚蛋白、兜甲蛋白和角蛋白10的表达没有改变。在体外，各种酒渣鼻触发因素降低了角质形成细胞中CLDN1、CLDN3和CLDN5的蛋白水平。综上所述，我们的研究结果表明CLDN而非其他皮肤屏障基因的表达显著降低，这可能与导致酒渣鼻发生的皮肤屏障受损有关。
Rosacea is a chronic inflammatory skin disorder whose pathophysiological mechanism remains largely unknown. Although recent studies have revealed the hypersensitivity of the skin towards chemical, thermal and biological stimuli, there is no direct molecular evidence suggesting the skin barrier is impaired in rosacea. In this study, we demonstrated that the mRNA levels of most claudins (CLDN), the main components of tight junctions determining the major barrier of the paracellular pathway between epithelial cells, were lowered in lesional skin of rosacea patients, especially with erythematotelangiectatic (ETR) and papulopustular (PPR) subtypes. Immunohistochemical analysis showed a significant decrease in the expression of CLDN1, CLDN3, CLDN4 and CLDN5 in the epidermis of ETR and PPR patients. However, the expression of other skin barrier genes, such as filaggrin, loricrin and keratin 10, was not altered. In vitro, various rosacea trigger factors reduced the protein levels of CLDN1, CLDN3 and CLDN5 in keratinocytes. Taken together, our results demonstrate a significant decrease in the expression of CLDN rather than other skin barrier genes, which may be associated with an impaired skin barrier responsible for the development of rosacea.