miR-5591靶向AGER/ROS/JNK抑制MSCs氧化应激损伤在糖尿病创面修复中的作用及机制

项目名称： miR-5591靶向AGER/ROS/JNK抑制MSCs氧化应激损伤在糖尿病创面修复中的作用及机制

项目编号： No.81501671

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： 李强

作者单位： 徐州医科大学

项目金额： 18万元

中文摘要： 糖尿病创面长期不愈，治疗困难。MSCs可促进创面修复，但在糖尿病患者体内，MSCs生物活性低。申请者预实验发现，AGEs/AGER诱导MSCs中ROS堆积，促进JNK磷酸化，导致MSCs氧化应激损伤，降低其生物活性。生物信息软件分析发现，以AGER3'UTR区为潜在靶序列的microRNA中，miR-5591分值最高。用AGEs处理miR-5591转染过的MSCs，发现miR-5591显著抑制AGER mRNA及蛋白表达，同时降低JNK磷酸化。由此提出：miR-5591可通过靶向沉默AGER表达，拮抗AGEs激活的AGER/ROS/JNK信号通路，保护MSCs抗氧化应激损伤，提高其生物活性，利于糖尿病创面修复。 .本研究将从细胞、分子及动物水平研究miR-5591靶向AGER/ROS/JNK信号对MSCs修复糖尿病慢性创面的影响及分子机制；为探寻有效的糖尿病创面治疗方法提供理论依据。

中文关键词： 糖尿病慢性创面；间充质干细胞；微小RNA；晚期糖基化终末产物受体

英文摘要： Diabetes chronic wounds don’t heal for a long time and is hard to treat. MSCs can promote wound repair, but have lower activity in diabetes patients. Our preliminary results showed that AGEs/AGER induced ROS accumulation, promoted JNK phosphorylation and resulted in MSCs oxidative injury. The biological information software showed that miR-5591 is the most likely microRNA within AGER 3 'UTR region for potential target sequence. AGEs treated MSCs transfected with miR-5591, AGER mRNA and protein level were down-regulated, p-JNK was inhibited. So, we suppose that miR-5591 inhibit AGER expression via combined with AGER 3 'UTR region, suppressing AGER/ROS/JNK signaling induced by AGEs, protecting MSCs antioxidative injury, improving MSCs biological activities and then promote diabetes chronic wounds healing.. This project will detect function and mechanism of miR-5591 target AGER/ROS/JNK signaling for diabetes chronic wounds repair by MSCs at cellular, molecular and animal levels, and will provide evidence for searching effective therapy for diabetes chronic wounds.

英文关键词： diabetes chronic wounds;mesenchymal stem cells;microRNA;advanced glycation end products receptor