miR-30d对肾间质纤维化进程中慢性炎症微环境的调控作用及机制研究

项目名称： miR-30d对肾间质纤维化进程中慢性炎症微环境的调控作用及机制研究

项目编号： No.81200496

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： 陈舜杰

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 肾间质纤维化（RIF）与恶性肿瘤相似都与慢性炎症微环境的形成与维持密切相关。miR-30d是癌基因的miRNA，促进肿瘤发生和发展，迄今对miR-30d与RIF的关系知之甚少。我们预实验提示RIF中的小管上皮细胞中高表达miR-30d，但其作用机制仍有待探讨。我们提出假说：在纤维化状态下，miR-30d通过作用小管上皮细胞、微环境内的免疫细胞从而诱生RIF。为了验证这一假说，我们制备miR-30d缺陷和高表达的HK-2细胞、miR-30d缺陷的UUO大鼠模型，采用real time PCR、Western blot、慢病毒载体转染、RNA干扰等手段，从分子、细胞、动物整体水平来探讨miR-30d在RIF进程中的重要作用，明确miR-30d通过诱导小管上皮细胞、"驯化"免疫细胞来调控RIF的机制。本研究将从miR-30d这个新视点为揭示RIF的机制奠定基础，为RIF的防治提供新的思路。

中文关键词： 急性肾损伤；急性肾损伤慢性转归；肾间质纤维化；microRNA；microRNA-204

英文摘要： Renal interstitial fibrosis (RIF) is closely related to the induction and maintenance of chronic inflammatory microenvironments, which interact with the malignant tumor through inflammatory mediators and immune signals to form a vicious cycle. miR-30ds are miRNAs that act as oncogenes and accelerate the induction and development of cancer. So far, little is known about the relationship between miR-30d and RIF. The findings from our preliminary experiment indicate that in renal tubular epithelial cells suffering renal interstitial fibrosis there is a persistent over-expression of miR-30d although the mechanism is yet to be explored. Therefore, we propose the hypothesis that where fibrosis exists, miR-30d will induce renal interstitial fibrosis by affecting the renal tubular epithelial cells and the immune cells in the microenvironment. To test the hypothesis and disclose how miR-30d regulates interstitial fibrosis by working on the renal tubular epithelial cells and the immune cells, we explored the significant role miR-30d played in the fibrosis of the renal interstitium from the molecular, cellular and "whole-animal" perspective, using a cell model with an under-expression of miR-30d and an over-expression of HK-2, a rat UUO model with an under-expression of miR-30d and employing real time PCR technology, Weste

英文关键词： Acute kidney injury；chronic-On-AKI；Tubulointerstitial Fibrosis；microRNA；microRNA-204