MiR-193b-3p/ERBB4轴调控角质形成细胞炎症因子表达参与银屑病致病的机制研究

银屑病是常见的炎症性皮肤病，其致病机理复杂。研究表明miRNA异常表达与银屑病发病密切相关。本课题组前期研究发现在银屑病炎症状态下，角质形成细胞（KC）中miR-193b-3p表达下调。此外，我们初步证实miR-193b-3p靶向ERBB4并抑制KC中炎症因子表达。但是，miR-193b-3p/ERBB4轴在银屑病发病过程中的作用机制仍不清楚。因此，本项目拟在前期研究基础上，以KC细胞、咪喹莫特诱导银屑病样小鼠以及皮肤特异性敲除miR-193b-3p的小鼠作为主要模型，结合银屑病患者临床样本，通过miRNA荧光原位杂交、免疫组化及流式细胞等技术，阐明“炎症/刺激-KC中miR-193b-3p/ERBB4轴-炎症因子-免疫细胞-炎症”这一正反馈循环对银屑病的致病作用。通过miRNA皮内注射技术验证miR-193b-3p在咪喹莫特小鼠模型中的疗效，以期为临床治疗银屑病提供新的理论基础。

Psoriasis is a common inflammatory skin disease, and its pathogenic mechanism is complicated. Studies have shown that abnormal expression of miRNA is closely related to the pathogenesis of psoriasis. Our previous study showed that the expression of miR-193b-3p in keratinocytes was down-regulated by psoriatic inflammatory condition. In addition, our preliminary data confirmed that miR-193b-3p targets ERBB4 and inhibits the expression of inflammatory factor in keratinocytes. However, the role and mechanism of miR-193b-3p/ERBB4 axis in psoriatic pathogenesis remains unclear. Therefore, this project intends to explore the specific role of miR-193b-3p involved in the pathogenesis of psoriasis by regulating ERBB4 expression, using HaCaT cell line, human primary foreskin keratinocytes, imiquimod-induced psoriasis-like mice, and skin-specific miR-193b-3p knockout transgenic mice as main models, combined with clinical samples from psoriatic patients. MicroRNA fluorescence in situ hybridization, immunohistochemistry staining, flow cytometry and other technologies are used to clarify the “Inflammation/Stimulation-miR-193b-3p/ERBB4 axis in keratinocytes-Inflammatory factors-Immune cells-Inflammation” positive feedback loop involved in psoriatic pathogenesis. Intradermal injection will be used to verify the therapeutic efficacy of miR-193b-3p in imiquimod-induced mouse model, with the aim of providing a new theoretical basis for clinical treatment of psoriasis.