银屑病发生发展过程中长链非编码RNA的筛选及其作用机制研究

项目名称： 银屑病发生发展过程中长链非编码RNA的筛选及其作用机制研究

项目编号： No.81472019

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈佳琦

作者单位： 浙江大学

项目金额： 80万元

中文摘要： 长链非编码RNA(long noncoding RNA, lncRNA)是长度超过200bp的ncRNA,参与基因的转录以及转录后水平的调控，在多种疾病发生发展过程中发挥重要的作用。银屑病是有遗传背景的、慢性复发性炎症性皮肤病。目前对银屑病研究的焦点主要集中在免疫异常的机理和银屑病易感基因定位上，对银屑病发生发展过程中哪些特异性lncRNA发挥调控作用，如何发挥作用，尚待阐明。本课题拟以银屑病发生发展过程中患者血液和皮肤为研究对象，通过离体、体外细胞学研究，特异性lncRNA转基因小鼠及基因敲除小鼠模型等研究，筛选鉴定出银屑病发生发展过程中及疗效相关的特异性lncRNA标记，阐明银屑病特异性lncRNA在银屑病角质形成细胞增殖、迁移、分化、凋亡、衰老中的作用及其机制，确立与银屑病发病相关的关键特异性lncRNA，探索针对这些lncRNA的抑制剂对银屑病的可能治疗作用。

中文关键词： 长链非编码RNA；银屑病；生物标志物

英文摘要： Long noncoding RNAs (long ncRNAs, lncRNAs) are non-protein coding transcripts longer than 200 nucleotides targeting nuclear chromatin and involve in transcriptional and post-transcriptional regulation. More and more studies have indicated the important role of lncRNAs in the pathogenesis of many kinds of diseases. Psoriasis is a common recurrent inflammation skin disease with genetic background. Till now, researches on the pathogenesis of psoriasis are mainly focused on the abnormal of immune system and the localization of susceptibility genes, it remains to be elucidated about which and how lncRNAs involving in the onset and development of psoriasis. This project is designed to screen the psoriasis-specific lncRNAs expressed in the blood and skin from psoriatic patients. Through ex vivo, in vitro cell function study and specific lncRNA transgenic mouse and knockout mouse, we try to define the critical psoriasis-specific lncRNAs, their roles in cell proliferation, migration, differentiation, apoptosis and senescence of epidermal keratinocytes, and finally, to investigate the possible therapeutic effect of inhibitors to the specific lncRNAs on psoriasis as markers.

英文关键词： long noncoding RNA;psoriasis;biomarker