Mucin-1/Wnt/β-catenin通路在高血压肾脏纤维化中的调控作用及机制研究

肾脏是高血压的重要靶器官之一。Mucin-1在肾小管上皮细胞高表达，可能通过某些机制导致上皮-间质转化（EMT），造成肾纤维化。Mucin-1过表达及在Galectin-3等因素作用下，可激活癌细胞内Wnt/β-catenin通路，而该通路激活与EMT效应物表达增加相关。Mucin-1很可能通过激活肾小管上皮细胞Wnt/β-catenin通路导致肾纤维化。我们前期在人尿蛋白质组学研究中发现，尿Mucin-1肽段与肾功能相关，但Mucin-1影响肾功能的机制尚未被阐明。本项目将在前期研究基础上，探讨：1）在SHR大鼠及β-catenin基因敲除小鼠中，Wnt/β-catenin通路介导Mucin-1导致肾纤维化过程；2）在肾小管上皮细胞中，Mucin-1/Wnt/β-catenin通路参与肾小管上皮细胞EMT机制；3）在高血压人群中，血、尿Mucin-1水平在慢性肾损伤中的作用。

Kidney is an important target organ of hypertension. Mucin-1 is highly expressed in the renal tubular epithelial cells and might cause epithelial-mesenchymal transition (EMT), resulting in renal fibrosis. Overexpress of Mucin-1 or Galectin-3 might activate Wnt/β-catenin signal passway which is associated with the increase of the EMT effector in cancer cells. Mucin-1 might induce renal fibrosis by activating Wnt/β-catenin pathway in the renal tubular epithelial cells. Our previous urinary proteomics study showed that urinary Mucin-1 subunit is associated with renal function in human while the mechanism is not demonstrated. Based on previous studies, this project will investigate: 1) In SHR rats and β-catenin knock-out mice, the progress of Wnt/β-catenin pathway in renal fibrosis caused by Mucin-1; 2) In renal tubular epithelial cells, the mechanism of Mucin-1/Wnt/β-catenin pathway in the EMT of renal tubular epithelial cells; 3) In hypertensive patients, the role of serum and urinary levels of Mucin-1 in renal damage.