Kim Yong-Eun, Cho Namjoon, Cheon Seonghye, Kim Kee K
Department of Biochemistry, Chungnam National University, Daejeon, 34134, Republic of Korea.
Department of Biochemistry, Chungnam National University, Daejeon, 34134, Republic of Korea.
Biochem Biophys Res Commun. 2017 Nov 4;493(1):744-750. doi: 10.1016/j.bbrc.2017.08.120. Epub 2017 Aug 30.
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Many studies investigating AD pathogenesis and its therapy have been conducted but none have been successful. One of the causes of AD is dysfunction of tight junctions through reduction of claudin 1 expression in the epidermal barrier of the skin. In the present study, we investigated the role of bortezomib (BTZ) in the restoration of the reduced expression of claudin 1. Immunoblot and immunofluorescence analyses revealed that BTZ increased the protein expression level of claudin 1 in the human keratinocyte cell line HaCaT, thereby forming paracellular barriers. Furthermore, repeated application of BTZ alleviated atopic symptoms on the backs and ears of 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice, and led to the formation of normal tight junctions in the epidermal barrier of DNCB-induced mice skin. Taken together, these results demonstrate that BTZ-induced claudin 1 expression may be a valuable therapeutic approach for AD.
特应性皮炎（AD）是一种慢性炎症性皮肤病。针对AD发病机制及其治疗方法已开展了许多研究，但均未取得成功。AD的病因之一是皮肤表皮屏障中claudin 1表达减少导致紧密连接功能障碍。在本研究中，我们探究了硼替佐米（BTZ）在恢复claudin 1表达降低方面的作用。免疫印迹和免疫荧光分析显示，BTZ可增加人角质形成细胞系HaCaT中claudin 1的蛋白表达水平，从而形成细胞旁屏障。此外，重复应用BTZ可减轻2,4-二硝基氯苯（DNCB）诱导的AD小鼠背部和耳部的特应性症状，并导致DNCB诱导的小鼠皮肤表皮屏障中形成正常的紧密连接。综上所述，这些结果表明，BTZ诱导的claudin 1表达可能是一种有价值的AD治疗方法。
