Cyr61对缺血性急性肾损伤后间质纤维化的影响及机制研究

项目名称： Cyr61对缺血性急性肾损伤后间质纤维化的影响及机制研究

项目编号： No.81470973

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： 徐岩

作者单位： 青岛大学

项目金额： 66万元

中文摘要： Cyr61是一种富含半胱氨酸的分泌蛋白，在缺血性急性肾损伤时由肾小管上皮细胞分泌进入肾小管和间质，对肾损伤有诊断价值，但它对肾损伤后间质纤维化的作用尚不明确。我们的研究结果显示:Cyr61对缺血性急性肾损伤具有一定的保护作用。为此，我们提出假说：Cyr61作为细胞外基质蛋白，可能通过抑制肾小管上皮细胞凋亡、诱导间质成纤维细胞的衰老凋亡、促进间质血管的生长、减缓间质纤维化进程。为了验证这一假说，我们将通过人肾小管上皮原代细胞、人肾间质成纤维原代细胞、人脐静脉内皮细胞和大鼠缺血性急性肾损伤模型，采用慢病毒载体转染、RNA干扰、ELISA、Western blot等手段，多方面探讨Cyr61在缺血性急性肾损伤后肾纤维化中的重要作用，明确Cyr61通过抑制内质网应激、调节细胞周期蛋白、促进血管内皮细胞增殖、出芽减缓肾损伤后间质纤维化。本研究将探讨Cyr61对缺血性急性肾损伤后肾间质纤维化的改善作用。

中文关键词： Cyr61；急性肾损伤；肾间质纤维化

英文摘要： Cyr61 is a cysteine-rich secretory protein, an immediate early gene product, which is secreted into the renal interstitial tubular epithelial cells in acute kidney injury. It has been proven valuable for the diagnosis of acute kidney injury, but its function in renal interstitial fibrosis follwing ischemic acute kidney injury is still not well known.Our previous research demonstrated that Cyr61 is protective for ischemia acute kidney injury.We propose that Cyr61, as a kind of extracellular matrix proteins, could delay renal interstitial fibrosis through inhibiting apoptosis of tubular epithelial cells, inducing apoptosis of interstitial fibroblasts and promoting growth of interstitial vascular. We established human renal tubular epithelial primary cells, human renal interstitial fibroblast primary cells, human umbilical vein endothelial cells and rat acute renal ischemic injury experimental models, through methods such as Lentiviral vector-transfection, RNA interference, ELISA, Western blot, to explore the function and mechanisim of Cyr61 in renal interstitial fibrosis following ischemic acute kidney injury by inhibiting endoplasmic reticulum stress, regulating cell cycle proteins, promoting vascular endothelial cell proliferation and sprouting, to provide experimental evidence for early intervention of renal interstitial fibrosis following ischemic acute kidney injury.

英文关键词： Cyr61;acute kidney injury;renal interstitial fibrosis