经典Wnt信号通路诱发EMT促进糖尿病视网膜病纤维化发生的机制

项目名称： 经典Wnt信号通路诱发EMT促进糖尿病视网膜病纤维化发生的机制

项目编号： No.81200706

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 周倜

作者单位： 中山大学

项目金额： 23万元

中文摘要： 糖尿病视网膜病纤维化增生是其致盲的基本病理表现。我们以往研究发现，经典Wnt信号通路在糖尿病视网膜病和肾病中过度激活，阻断Wnt信号通路可以减弱组织纤维化，提示Wnt信号通路激活促进纤维化发生，但机制尚不清楚。EMT发生与肾脏、肺脏以及肝脏纤维化紧密相关，而EMT是否介导糖尿病视网膜病的纤维化尚未报导；我们的预实验结果初步显示糖尿病视网膜病存在EMT；本项目拟进一步证实糖尿病视网膜病中EMT的发生并阐明EMT导致视网膜纤维化发生的机制。另一方面，Wnt信号通路是介导EMT的主要信号通路，我们以往研究显示Wnt信号通路的激活，预实验结果进一步提示Wnt激活可引起视网膜色素上皮细胞发生EMT；本项目拟阐明Wnt信号通路诱发视网膜EMT发生的机制。旨在明确Wnt信号通路过度激活通过诱发EMT促进糖尿病视网膜病视网膜纤维化，对于充分理解糖尿病视网膜病纤维化发病机制和寻找有效治疗靶点具有重要价值。

中文关键词： 糖尿病视网膜病；上皮间充质转化；高糖；视网膜色素上皮；Müer细胞

英文摘要： Fibrosis is main pathological characteristic of blindness in diabetic retinopathy. Our previous studies have shown that the canonical Wnt signaling pathway is activated in diabetic retinopathy and nephropathy in animal models of diabetes and blockade of the canonical Wnt signaling pathway attenuates tissue fibrosis, strongly suggesting the activation of canonical Wnt signaling pathway promotes fibrosis. However, the mechanism is still unclear. EMT is closely related to the fibrosis in kidney, lung and liver,while whether the EMT is involved in the fibrosis of diabetic retinopathy has not been reported. Our preliminary results indicate the occurrence of EMT in experimental diabetic retinopathy. This study is designed to further prove the EMT occurrence in diabetic retinopathy and clarify the mechanism responsible for EMT in retina fibrosis. On the other hand, Wnt signaling pathway mediates EMT and Our preliminary results show that activation of canonical Wnt signaling pathway can cause retinal pigment epithelial cells to undergo EMT. Therefore, this study is also to enlucidate the mechanism by which the canonical Wnt signaling pathway induces EMT in diabetic retinopathy. The purpose of this project is to elucidate the canonical Wnt signaling pathway mediated-EMT promotes retinal fibrosis of diabetic retinopathy

英文关键词： Diabetic retinopathy；Epithelial-mesenchymal transition (EMT)；Hyperglycaemia；Retinal Pigment Epithelium (RPE)；Müer cells