高血压性肾损害，是我国终末期肾病的主要病因，而肾小管间质纤维化，是其重要的病理基础，但临床上仍缺乏有效的治疗方法。在肾小管间质纤维化的过程中，肾小管上皮细胞向间叶细胞转化(EMT)，继而导致细胞外基质(ECM)过度沉积，是其中的关键环节。预实验结果提示，氯离子通道TMEM16A在小鼠肾脏的肾小管中高表达，但在高血压病理状态下却显著降低；与此同时，肾小管EMT标记蛋白α-SMA和ECM组分Fibronectin的表达却明显增强。由此，我们推测TMEM16A介导了高血压诱导的肾小管间质纤维化，而其作用可能与抑制Wnt/β-catenin信号通路有关。本课题拟：明确TMEM16A参与高血压诱导的肾小管EMT，阐明TMEM16A通过Wnt/β-catenin信号通路抑制肾小管EMT，继而改善高血压诱导的肾小管间质纤维化，为评估TMEM16A可否作为防治肾小管间质纤维化的药物新靶点提供实验依据。

Hypertension nephropathy (HN), characterized by tubulointerstitial fibrosis (TF), is major cause of end-stage renal disease in China. Currently, treatment options for HN are limited..Tubular epithelial–myofibroblast transdifferentiation (TEMT) is an important event during progressive renal TF, which leads to loss of epithelial cell adhesion and subsequently excessive accumulation of extracellular matrix (ECM) protein. Our preliminary results showed that the expression of TMEM16A was downregulated; meanwhile, the expression of α-SMA and Fibronectin were upregulated, suggesting that TMEM16A implicated with TF during the development of HN. In this study, we will test the hypothesis that TMEM16A inhibits TEMT and suppresses renal TF via Wnt/β-catenin signaling. The result of this study will enable us to evaluate the feasibility of using TMEM16A as a therapeutic target for renal TF.