Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, China.
J Dermatol. 2019 Apr;46(4):314-321. doi: 10.1111/1346-8138.14792. Epub 2019 Feb 4.
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.
酒渣鼻是一种慢性炎症性皮肤疾病，其病理生理机制在很大程度上尚不清楚。尽管最近的研究表明皮肤对化学、热和生物刺激的敏感性增加，但没有直接的分子证据表明酒渣鼻的皮肤屏障受损。在这项研究中，我们证明了大多数紧密连接蛋白（CLDN）的 mRNA 水平在酒渣鼻患者的皮损皮肤中降低，尤其是在红斑毛细血管扩张（ETR）和丘疹脓疱（PPR）亚型中。免疫组织化学分析显示，在 ETR 和 PPR 患者的表皮中，CLDN1、CLDN3、CLDN4 和 CLDN5 的表达显著下降。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。总之，我们的结果表明 CLDN 的表达显著下降，而不是其他皮肤屏障基因，这可能与皮肤屏障受损有关，导致酒渣鼻的发生。
