miR-199a靶向HIF-1α调控表皮细胞的增殖参与银屑病的发病机制

MIR-199A TARGETING HIF-1 ALPHA REGULATES THE PROLIFERATION OF EPIDERMAL CELLS IN PSORIASIS AND ITS PATHOGENESIS

目的探讨miR-199a靶向低氧诱导因子-1α(HIF-1α)调控表皮细胞的增殖参与银屑病的发病机制,以此为临床银屑病治疗提供靶点。方法选取2014年1月-2017年10月我院收治的22例寻常性银屑病患者皮损区组织作为观察组,以自愿参与课题的21例健康体检者皮肤组织为对照组。对二组受试者检测miR-199a以及HIF-1α的表达差异,以此为依据分析miR-199a是否具有靶向调控HIF-1α的作用。然后验证miR-199a与HIF-1α的靶向结合关系,主要包括在人永生化表皮细胞中将miR-199a mimics转染,采用Western blot检测HIF-1α的蛋白表达水平以及通过利用双荧光素酶报告基因实验。最后通过MTT法作为检测手段探究银屑病的发病机制,主要依据为miR-199a以及HIF-1α对人永生化表皮细胞增殖的影响。结果通过对正常体检者以及寻常性银屑病患者皮损区检查发现,随着miR-199a的表达下调,HIF-1α的表达呈上调状态,统计学分析miR-199a与HIF-1α存在负相关性。在人永生化表皮细胞中转染miR-199a mimics,发现具有下调HIF-1α表达的作用,与上述研究结果一致。HIF-1α可恢复miR-199a对人永生化表皮细胞增殖的抑制作用。结论银屑病的发病机制研究中发现miR-199a靶向HIF-1α调控表皮细胞的增殖,是银屑病发病的重要因素,同时值得临床在制定相应治疗手段时借鉴此依据。

Objective To investigate the pathogenesis of psoriasis mediated by miR-199a targeting HIF-1α in regulating epidermal ceil proliferation.Methods The skin lesions of 22patients with psoriasis vulgaris treated in author's hospitaI from January 2014to October 2017were selected as the observation group.The skin of 21healthy volunteers voluntarily participating in the task was selected as the control group.Two groups of subjects were detected miR-199a and HIF-la differences in expression,based on which miR-i99a has targeted regulation of HIF-1α lpha role.The targeted binding of miR-199a to hypoxia-inducible factor-1α (HIF-1α)was then validated.These include transfeetion of miR-199a mimics in immortalized human epidermal cells,detection of HIF-1α protein expression by Western blot,and by dual luciferase reporter assays.Finally,MTT assay was used to explore the pathogenesis of psoriasis,mainly based on the impact of miR-199a and HIF-1α on human immortalized epidermal cell proliferation.Results The examination of the lesions in normal and psoriasis patients showed that miR-199a was downregulated in HIF-1α lpha and it was negative correlated to HIF- 1α lpha.Transfection of miR-199a mimics in human immortalized epidermal cells was found to have a downregulation of HIF-1α expression,consistent with the above findings.HIF-1α restores the inhibitory effect of miR- 199a on human immortalized epidermal cell proliferation.Conclusion The study of the pathogenesis of psoria- sis shows that miR-199a targeting HIF-1α regulates the proliferation of epidermal cells and is an important factor in the pathogenesis of psoriasis.At-the same time,it is worth to draw reference from the clinical treatment of appropriate means.