糖尿病肾病(DN)已成为导致慢性肾衰竭的主要原因，发病机制复杂且尚无有效治疗措施。肾小管-间质纤维化是DN进行性发生发展的关键因素，而Wnt信号通路活化在肾小管-间质纤维化中具有重要作用，但调控机制未充分明确。研究显示，尾型同源盒转录因子-2(Cdx2)可能对Wnt/β-catenin通路有负调控作用，但Cdx2在DN发病中的作用及机制未见报道。我们近期发现，DN肾小管上皮细胞中Cdx2蛋白表达减少，过表达Cdx2可抑制Wnt/β-catenin通路，推测Cdx2对Wnt/β-catenin通路的负调控作用减弱可促进DN肾纤维化。因此，本项目拟以Cdx2转基因糖尿病小鼠和高糖培养的肾小管上皮细胞为研究对象，采取基因敲低、过表达及抑制实验，探讨Cdx2负调控Wnt/β-catenin通路对抗肾纤维化效应的作用和机制，为进一步认识DN肾纤维化的发病机制及探寻新的有效治疗靶点提供实验依据。

Diabetic nephropathy(DN)is the leading cause of chronic renal failure,which has complicated pathogenesis and lacks of effective treatment.The over activated Wnt signal pathway plays an important role in tubulointerstitial fibrosis,and it is the key factor in the process of DN with an unclearly regulation mode.Research shows that the caudal typehomebox transcription factor 2(Cdx2)may act as a negative regulator of the Wnt/β-catenin pathway.However, functions and mechanisms of Cdx2 in DN have not yet been reported.We recently found that the expression of Cdx2 protein was reduced and overexpression of Cdx2 could inhibit the Wnt/β-catenin pathway, which suggested that the attenuated effect of Cdx2 negatively regulating Wnt/β-catenin pathway can promote the development of renal interstitial fibrosis in DN.Taking transgenic mice with Cdx2 gene and renal tubular epithelial cells under high-glucose cultivation as the study subjects, we intend to knockdown or over-express of Cdx2 gene or apply inhibitors to explore the mechanisms of Cdx2 negatively regulating Wnt/β-catenin pathway against renal fibrosis.This may provide an updated understanding of underlying pathogenesis mechanisms, and explore a novel and promising therapeutic target for DN.