CaSR活化对肾小管上皮细胞胞外基质形成的影响及机制研究

项目名称： CaSR活化对肾小管上皮细胞胞外基质形成的影响及机制研究

项目编号： No.81500545

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： 伍敏

作者单位： 东南大学

项目金额： 18万元

中文摘要： 细胞外基质（ECM）过度沉积是导致肾脏纤维化进展的关键因素，探讨ECM调控机制对于肾脏纤维化防治具有重要意义。近期研究发现，CaSR激动剂具有抑制ECM异常沉积并改善肾脏纤维化的作用。但目前有关小管上皮细胞CaSR活化对肾小管间质纤维化过程中ECM形成的影响和机制仍不清楚。我们的前期研究发现，CaSR激动剂具有减轻慢性肾衰大鼠小管细胞损伤，降低小管区ECM蛋白和β-catenin表达的作用。基于上述工作基础，我们提出本研究假说：肾小管上皮细胞CaSR活化可通过调节胞内β-catenin径路，减轻损伤因素所致肾小管上皮细胞ECM的生成和/或促进ECM降解，从而抑制小管间质纤维化。本课题拟在前期工作基础上，通过体内外实验观察肾小管上皮细胞CaSR活化对ECM形成和降解的影响，以阐明CaSR激动剂改善肾小管上皮细胞损伤及小管间质纤维化的作用机制，为临床防治慢性肾衰竭提供新的思路和干预靶点。

中文关键词： 慢性肾脏病；肾小管上皮细胞；钙敏感受体；细胞外基质

英文摘要： Excessive deposition of extracellular matrix (ECM) is known to be the key determinant for the progression of renal fibrosis. Thus, investigations on the regulatory mechanisms of ECM formation are important for the prevention and treatment of renal fibrosis. In recent studies, calcium sensing receptor (CaSR) agonist has been found to be effective in reducing the extent of ECM deposition and renal fibrosis. However, the effect of CaSR activation at renal tubular epithelial cell level on tubulointerstitial fibrosis is still unknown. As our previous data shown, CaSR agonist could significantly attenuate renal epithelial injury and decrease the expression of ECM protein and β-catenin in tubular area. Based on these findings, we proposed the hypothesis: activation of CaSR on renal tubular epithelial cell could inhibit the synthesis of ECM and enhance the degradation of ECM through the regulation of intracellular β-catenin pathway. In this study, we plan to investigate the effeicacy of tubular epithelial CaSR activation on ECM and its possible molecular pathway by in vivo and in vitro experiments. The results of this study may shed light on mechanisms underlying the renoprotective role of CaSR agonist and may provide novel ideas for the potential therapeutic target for chronic kidney disease.

英文关键词： chronic kidney disease;tubular epithelial cell;CaSR;ECM