一个功能未知miRNA----miR-4330在子痫前期中作用与机制的研究

miR-4330 expression was significantly down-regulated in preeclampsia placenta vascular by the miRNA microarray screening. Our previous study found that : the construction response of placenta vascular smooth muscle(VSMCs) was significantly higher while silencing of miR-4330; bioinformatic analysis and experiments predicted that angontensin Ⅱreceptor-1(AGTR1) was its target gene; The expression of AGTR1 was upregulated noticeably in the VSMCs of the placenta in preeclampsia, and upregulated in the VSMCs with downregulated miR-4330; Based on these results, we suggested that miR-4330 may participate in the progress of preeclampsia through AGTR1. In our project, we will choose the clinical specimens, then evaluate the relation between miR-4330 and the function of placenta vascular; further evaluate the effect of miR-4330 on the placental vascular function with the overexpression and silencing strategies; than taking AGTR1 as the clue, by rescue experiments and luciferase reporter experiment, we will fully demonstrate the mechanism of miR-4330 involved in the mechanism of PE through regulating its target gene of AGTR1. The biological function of miR-4330 is still unknow, if successful, we will provide a new target for the prevention and control of PE.

miR-4330是我们应用miRNA芯片筛选获得的、在子痫前期（PE）胎盘血管中低表达、在PE中功能未知的miRNA。前期发现：miR-4330表达沉默显著增强胎盘血管平滑肌细胞（VSMCs）收缩功能；生物信息学和实验初步证实血管紧张素Ⅱ-1型受体AGTR1为miR-4330的靶基因；AGTR1高表达于PE胎盘VSMCs中，且在miR-4330沉默的VSMCs中表达上调，提示miR-4330可能通过AGTR1参与PE的发生。本课题拟选取临床标本，评估miR-4330与胎盘血管功能关系；通过过表达与沉默策略，进一步评估miR-4330对胎盘血管功能的影响；并以AGTR1为线索，通过挽救实验和萤光素酶报告实验，充分论证miR-4330通过调控AGTR1参与PE发生的机制。目前尚无miR-4330在PE中的研究报道，本研究如获成功，有望为PE防治提供新靶标。

miR-4330是我们应用miRNA芯片筛选获得的、在子痫前期（PE）胎盘血管中低表达、在PE中功能未知的miRNA。前期研究提示miR-4330可能通过AGTR1参与PE的发生。本项目通过对miR-4330在胎盘血管中的表达及其与AGTR1、血管功能之间的相关性研究；miR-4330过表达、表达沉默对HUVSMCs收缩功能的影响研究； miR-4330调控血管AGTR1表达及参与子痫前期发病的分子机制的探索性研究。系统论证了“miR-4330可能通过调控AGTR1 影响VSMCs 的收缩功能而参与子痫前期的发生”这一科学问题。目前尚未见任何有关miR-4330 生物学功能的报道，本申请项目具有源头创新性，可能为阐明子痫前期的发病机制，并为子痫前期及其严重并发症的防治提供新的、潜在的干预靶标。在本项目资助下，课题组已发表1 篇中文文章、1 篇SCI 论文， 1 篇SCI 论文已投稿，还有1 篇SCI正在撰写中；参与发表2篇SCI论文。协助培养了1名硕士研究生，已完成论文答辩、顺利毕业。