microRNA-200b 调控KLF-10/Treg 影响动脉粥样硬化的作用与机制研究

项目名称： microRNA-200b 调控KLF-10/Treg 影响动脉粥样硬化的作用与机制研究

项目编号： No.81500338

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 何少林

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 动脉粥样硬化（AS）是一种慢性炎症性疾病。调节性T细胞（Treg）在AS进程中发挥重要作用，但在AS中Treg活化、分化与功能的确切机制不明。KLF-10可直接促进Treg活化、分化与功能，进而抑制AS，但其上游调节机制知之甚少。我们前期结果发现：生物信息学预测提示miR-200b靶基因为KLF-10；外源性增加Treg内miR-200b可明显抑制KLF-10及foxp3表达；急性冠脉综合症者血中miR-200b表达与KLF-10，foxp3水平及Treg数量负相关，提示miR-200b可能靶向调控KLF-10，进而调节Treg细胞，最终影响AS进程。为此，本项目拟进一步证实miR-200b的直接靶基因是否为KLF-10，miR-200b是否参与抑制Treg细胞活化、分化与功能，进而影响AS进程。结果将有助于阐明AS进程中Treg上游调控新机制，为AS早期诊断与治疗提供新靶点。

中文关键词： 调节性T细胞；动脉粥样硬化；微小RNA；核转录因子

英文摘要： Atherosclerosis is a multifactorial chronic inflammatory disease perpetuated by immune cells and cytokines.CD4+CD25+ regulatory T cells (Treg) play a major role in the maintenance of atherosclerosis,although the mechanisms controlling Treg development and suppressor function remain incompletely understood.Kruppel-like factor 10 (KLF10) constitutes an important regulator of both T regulatory cell suppressor function and atherosclerotic lesion formation through distinct mechanisms involving foxp3，but the upstream mechanisms controlling KLF10 are limited. Our recent data reveals that:bioinformatics analysis indicated that KLF10 may be the target gene of miR-200b;further study confirmed that overexpression of miR-200b in Treg can inhibit expression of KLF10 and foxp3;on the other hand,we find that miR-200b expresison increased, but the KLF10 and foxp3 expression decreased accompanied with less Treg numbber in peripheral blood mononuclear cells from acute coronary syndromen patients.So we raise a hypothesis that miR-200b promotes atherosclerosis by inhibitting Treg development and suppressior function via downregulation of KLF10 post-transcriptionally.Next we will verify that whether KLF10 is the direct target genen of miR-200b and whether the development and suppressor function fo Treg inhibited by miR-200b can promote inflammation in atherosclerosis. With these effort, we can provide novel insights into the upstream controlling of Treg ,leading to new therapeutic approches and targets in prevention and treatment of atherosclerosis.

英文关键词： microRNA-200b;KLF-10;Treg;Atherosclerosis