新疆哈萨克族和汉族原发性高血压炎症应答相关非编码RNA的筛选及其表观遗传调控机制研究

Hypertension is now considered a chronic inflammatory disease, and is also accompanied by continuous and low-grade activation of the adaptive immune system and release of pro-inflammatory cytokines, thus leading to infiltration of inflammatory cells in target organ and functional damage of target organ. Recent evidence indicates that non-coding RNAs have an important regulatory role in inflammatory response and during development of hypertension. However, which specific non-coding RNAs and regulation network between non-coding RNAs and mRNAs are involved in hypertension mediated inflammatory response remain largely undefined. Accordingly, we will investigate the LncRNAs (long non-coding RNAs) and circRNAs (Circular RNAs) expression differences in peripheral blood PBMC of Kazakh patients in Xinjiang with essential hypertension (EH) that have a high prevalence of hypertension, and Han EH patients using microarray analysis. Moreover, we will also analyze the relationship of targeted regulation between differentially expressed non-coding RNAs (LncRNAs and circRNAs) and differentially expressed microRNAs according to our previous study, and the relationship between non-coding RNAs and their target mRNAs via bioinformatics analysis and molecular biological techniques (Quantitative real time polymerase chain reaction, dual-luciferase assays, Western blot). Finally, the key correlation networks of LncRNAs/circRNAs-microRNAs-mRNAs associated with hypertension mediated inflammatory response in EH patients of Kazakh or Han populations, and the underlying molecular mechanism of these LncRNA/circRNA-microRNA-mRNA co-expression networks in modulating hypertension mediated inflammatory response in EH patients of Kazakh or Han populations will be elucidated according to the common target microRNAs of the LncRNAs/circRNAs and mRNAs.

高血压作为一种慢性炎症性疾病，发病过程中伴随着适应性免疫系统的持续低度激活及炎症因子释放，从而引起靶器官的炎性浸润和功能损伤。近期研究表明非编码RNA在炎症应答和高血压的发生发展中具有重要调控作用。然而，哪些非编码RNA及其靶向调控网络参与了高血压炎症反应尚不清楚。因此，本项目拟以高血压发病率较高的新疆哈萨克族原发性高血压患者，以及汉族原发性高血压患者的外周血PBMC为研究对象，采用LncRNA和circRNA芯片筛选并建立新疆哈萨克族和汉族高血压炎症发生相关的非编码RNA差异表达谱；并结合前期microRNA芯片筛选分析结果，运用生物信息学及分子生物学技术探索差异表达非编码RNA之间及其与靶基因之间的靶向调控关系，初步阐明引起哈萨克族和汉族原发性高血压炎症应答的关键LncRNA/circRNA-microRNA-mRNA调控网络及其调控哈族和汉族高血压炎症应答的分子机理。

高血压作为一种慢性炎症性疾病，发病过程中伴随着适应性免疫系统的持续低度激活及炎 症因子释放，从而引起靶器官的炎性浸润和功能损伤。近期研究表明非编码RNA在炎症应答和高血压的发生发展中具有重要调控作用。然而，哪些非编码RNA及其靶向调控网络参与了高血压炎症反应尚不清楚。我们的研究发现：（1）新疆哈萨克族原发性高血压患者外周血PBMC中LncRNAs、mRNAs、circRNAs存在差异，主要参与局部黏附、细胞黏附分子、自适应免疫系统、趋化因子信号通路、白细胞跨内皮迁移、细胞因子与其受体相互作用、B细胞受体信号通路、血小板活化、cAMP信号通路等炎症应答相关信号通路。（2）新疆汉族原发性高血压患者外周血PBMC中LncRNAs、mRNAs和circRNAs的表达存在差异，主要参与AMPK信号通路、缝隙连接、NF-κB信号通路、自适应免疫系统、EGFR信号传导、PI3K-Akt信号通路、层粘连蛋白相互作用等炎症应答相关信号通路。（3）新疆哈萨克族和汉族原发性高血压的发生中存在潜在ceRNA调节机制。