| Autor: |
Zu Y; School of Mechanical and Material Engineering, North China University of Technology, No. 5 Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, People's Republic of China. zuyan@foxmail.com., Chen XF; Beijing Institute of Astronautical System Engineering, Beijing, 10076, People's Republic of China., Li Q; School of Mechanical and Material Engineering, North China University of Technology, No. 5 Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, People's Republic of China., Zhang ST; School of Mechanical and Material Engineering, North China University of Technology, No. 5 Jinyuanzhuang Road, Shijingshan District, Beijing, 100144, People's Republic of China. |
| Abstrakt: |
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 Ca 2+ (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. |
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