miR-107调控系膜细胞和糖尿病肾病大鼠PARP-1表达的分子机制研究

项目名称： miR-107调控系膜细胞和糖尿病肾病大鼠PARP-1表达的分子机制研究

项目编号： No.81470953

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 姜宗培

作者单位： 中山大学

项目金额： 73万元

中文摘要： 多元醇途径、糖基化终产物、蛋白激酶C以及己糖氨途径是公认的糖尿病肾病（DN）四个重要损伤机制。但单一阻断其中任一途径并未取得理想疗效。我们上一个国家自然科学基金研究发现，高糖及AngII可促进氧化应激反应并诱导多聚ADP核糖聚合酶-1（PARP-1）表达和激活，从而激发上述四条损伤途径，引发一系列糖尿病并发症，因此PARP-1过表达被视为DN的共同发病机制。但调控PARP-1的分子机制和信号通路尚不明确。我们前期研究首次发现小鼠肾脏系膜细胞能表达miR-107，高糖可下调系膜细胞miR-107表达，其表达与PARP-1过表达呈负相关；miR-107可能是调控PARP-1表达，参与DN发病的关键因子。为此，在本课题中，我们将通过抑制和上调miR-107在小鼠系膜细胞中和糖尿病大鼠肾脏组织中的表达，探索miR-107调控DN PARP-1表达的分子机制，阐明其在DN发病机制及防治中的关键作用。

中文关键词： miR-107；多聚ADP；核糖聚合酶；糖尿病肾病；甘油醛-3-磷酸；多元醇途径

英文摘要： Polyol pathway, advanced glycation end products (AGEs) pathway, protein kinase C pathway and hexose ammonia pathway are recognized as the fourth important injury mechanism. But, blocking either way did not achieve good results. Our previous NSFC study found that high glucose and AngII can promote the oxidative stress, and induce Poly ADP-ribose polymerase -1 (PARP-1) activation,following by regulating these four important damage pathways, triggering a series of complications of diabetes.Therefore, PARP-1 overexpression is regarded as a common pathogenesis of DN. However, the molecular mechanisms and signal pathways are not clear. Our previous study also found that miR-107 expression could be expressed in mesangial cells, and its expression was negatively correlated with PARP-1 expression. So, miR-107 may regulate the expression of PARP-1, and acts as the key factors involved in the pathogenesis of DN. In this study, we will up-regulate and down-regulate the miR-107 expression in mesangial cells in mice and kidney tissue of diabetic rats, and observed the regulating role of miR-107 in the expression of PARP-1 in DN diseases, to clarify its key role in the pathogenesis and prevention of DN.

英文关键词： miR-107;PARP-1;Diabetic nephropathy;Glyceraldehyde-3 - phosphate;Polyol pathway