Atopic dermatitis (AD) is a chronic inflammatory skin disease influencing not only children but also adults. It is well-known that AD has a complex pathogenesis without effective therapy. Herein, we explored the function and mechanism of CYT387, a novel JAK2 inhibitor, on epidermal barrier damage. HaCaT cells exposed with high-concentration Ca²⁺ (1.8 mM) for 14 days were recruited for the model of keratinocytes (KC). The cell model of skin barrier damage was induced by IL-13, and KC markers such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL) were detected to judge the success of the model. In this study, we found that miR-143 was lowly expressed whereas IL-13Rα1 was highly expressed in blood cells of patients with AD, indicating their negative correlation. Moreover, IL-13 treatment down-regulated miR-143 and up-regulated activated JAK2 and STAT3 phosphorylation, which was reversed by CYT387 administration. The dual-luciferase reporter assay verified that miR-143 could directly bind to 3′-UTR of IL-13Rα1, as well as STAT3. Furthermore, the function of CYT387 in the skin barrier damage induced by IL-13 was abolished by miR-143 inhibitor. Thus, CYT387 might alleviate IL-13-induced epidermal barrier damage via targeting IL-13Rα1 and STAT3 by miR-143 to repress inflammation. These findings revealed that the protective effects and the underlying mechanisms of CYT387 in AD, which provided evidence that miR-143 may be a novel therapeutic target for AD.

特应性皮炎（AD）是一种慢性炎症性皮肤病，不仅影响儿童，而且影响成年人。众所周知，AD没有有效的治疗方法就具有复杂的发病机理。在本文中，我们探讨了新型JAK2抑制剂CYT387对表皮屏障损伤的功能和机制。暴露于高浓度Ca ^2+的HaCaT细胞（1.8 mM）连续14天募集用于角质形成细胞（KC）的模型。IL-13诱导了皮肤屏障损伤的细胞模型，并检测了KC标记，例如丝蛋白（FLG），loricrin（LOR）和involucrin（IVL）来判断模型是否成功。在这项研究中，我们发现在AD患者的血细胞中miR-143的表达较低，而IL-13Rα1的表达较高，表明它们之间呈负相关。此外，IL-13处理下调了miR-143，并上调了激活的JAK2和STAT3磷酸化，这可以通过CYT387的给药来逆转。双重荧光素酶报告基因检测证实，miR-143可以直接与IL-13Rα1的3'-UTR以及STAT3结合。此外，miR-143抑制剂消除了CYT387在IL-13诱导的皮肤屏障损害中的功能。从而，CYT387可能通过miR-143靶向IL-13Rα1和STAT3来减轻炎症反应，从而减轻IL-13诱导的表皮屏障损伤。这些发现揭示CYT387在AD中的保护作用及其潜在机制，这提供了miR-143可能是AD的新型治疗靶标的证据。