RelB/DNMT3a介导RBM3启动子区DNA甲基化在模拟失重致血管内皮细胞功能改变中的作用和机制研究

航天员的立位耐力降低和运动能力下降等心血管功能失调症状是失重带来的健康问题之一。文献报道失重条件下血管内皮细胞形态和功能改变是心血管功能失调的重要原因，我们前期发现模拟失重效应促进血管内皮细胞凋亡和迁移等，然而导致这些改变的关键分子仍未阐明。我们通过RNA测序筛选出模拟失重下血管内皮细胞中的差异表达基因RBM3，利用CpG岛预测工具和去甲基化试剂，推测RBM3低表达是由于启动子区高甲基化，而模拟失重下增多的RelB作为转录因子可能促进DNMT3a的表达进而使RBM3启动子区高甲基化，改变细胞功能。本课题拟利用RNAi、染色质免疫共沉淀等技术探讨模拟失重效应下RelB/DNMT3a与RBM3基因启动子区DNA高甲基化的关系，揭示RBM3在失重下血管内皮细胞凋亡、蛋白合成、迁移等功能中的作用。该研究有助于理解失重条件下血管内皮细胞的表观遗传学调控机制，为航天员心血管功能不良的防护提供新思路。

The cardiovascular dysfunction including orthostatic intolerance and disability on physical exercise is one of the health problems for astronauts induced by spaceflight. It is reported that morphological and functional changes play a pivotal role in cardiovascular dysfunction. We have found previously that simulated microgravity induces apoptosis and enhances cell migration. However, the underlying key molecules have not been uncovered. Differentially expressed gene RBM3 was selected through RNA-seq. Prediction of potential CpG island using public online tool and treatment with the DNA demethylating agent indicated that downregulation of RBM3 gene may be due to the hypermethylation of its promoter. The increase of RelB may promote the expression of methyltransferase DNMT3a which may promote the methylation of the RBM3 promoter under simulated microgravity, thus regulating vascular endothelial function. This research aims at detecting the relationship between RelB/DNMT3a and DNA methylation in the RBM3 promoter region under simulated microgravity and clarifying the role of RBM3 expression in apoptosis, protein synthesis and cell migration and so on. This research will deepen the understanding of epigenetic regulations in endothelial functional changes under microgravity and help to provide potential therapeutic actions to protect cardiovascular system in astronauts.