Fu Dandan, Yu Wenfa, Li Min, Wang Huimin, Liu Dong, Song Xiangfeng, Li Zhanguo, Tian Zhongwei
Department of Dermatology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453000, Henan, China.
Department of Otolaryngological, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453000, Henan, China.
Immunol Lett. 2015 Jul;166(1):55-62. doi: 10.1016/j.imlet.2015.05.014. Epub 2015 Jun 1.
Psoriasis is a common chronic inflammatory and T cell-meditated autoimmune skin disease. A recent study found that Runt-related transcription factor 3 (RUNX3) is a susceptibility gene for psoriasis; however, its biological role in the disease has not been studied. RUNX3 was predicted to be the target gene of microRNA-138 (miR-138). The current research was designed to delineate the mechanism of miR-138 in regulating psoriasis via targeting RUNX3. In this study, we found that the expression of RUNX3 is increased significantly while the expression of miR-138 decreased significantly in CD4(+) T cells from psoriasis patients. Moreover, the luciferase report confirmed the targeting reaction between miR-138 and RUNX3. After transfection with the miR-138 inhibitor into CD4(+) T cells from healthy controls, we found that the inhibition of miR-138 increases RUNX3 expression and increased the ratio of Th1/Th2. Furthermore, the miR-138 mimic was transfected into CD4(+) T cells from psoriasis patients. The results showed that the overexpression of miR-138 inhibits RUNX3 expression and decreased the ratio of Th1/Th2 in CD4(+) T cells. Taken together, our study suggests that increased miR-138 regulates the balance of Th1/Th2 through inhibiting RUNX3 expression in psoriasis, providing a potential therapeutic target for psoriasis.
银屑病是一种常见的慢性炎症性且由T细胞介导的自身免疫性皮肤病。最近一项研究发现， runt相关转录因子3（RUNX3）是银屑病的一个易感基因；然而，其在该疾病中的生物学作用尚未得到研究。RUNX3被预测为微小RNA-138（miR-138）的靶基因。当前的研究旨在阐明miR-138通过靶向RUNX3来调节银屑病的机制。在本研究中，我们发现银屑病患者CD4(+) T细胞中RUNX3的表达显著增加，而miR-138的表达显著降低。此外，荧光素酶报告实验证实了miR-138与RUNX3之间的靶向反应。在用miR-138抑制剂转染健康对照者的CD4(+) T细胞后，我们发现抑制miR-138可增加RUNX3的表达并提高Th1/Th2的比例。此外，将miR-138模拟物转染到银屑病患者的CD4(+) T细胞中。结果显示，miR-138的过表达抑制了RUNX3的表达，并降低了CD4(+) T细胞中Th1/Th2的比例。综上所述，我们的研究表明，在银屑病中，miR-138的增加通过抑制RUNX3的表达来调节Th1/Th2的平衡，为银屑病提供了一个潜在的治疗靶点。
