糖尿病肾病(DN)是糖尿病最常见的并发症，也是导致终末期肾病的主要原因。目前研究指出上皮间质转化(EMT)可能参与了DN肾间质纤维化过程，但由于缺乏可靠的DN动物模型，体内研究结果存在诸多争议，我们前期研究结果显示，在血压正常的DN猴模型肾组织内EMT标志物E-cadherin表达上调，这与临床DN病人的检测结果正好相反，而在合并高血压的DN猴模型肾组织内E-cadherin表达呈现下调趋势。基于上述认识和工作基础，我们提出“高血压可通过调控与EMT发生密切相关的功能基因，来促进DN肾间质纤维化过程中肾小管上皮细胞EMT的发生”这一新的科学假设。为证明该科学假设，本课题将通过药物诱发建立新型糖尿病肾病合并高血压猴模型，并利用该模型结合体内外实验，进一步探讨DN肾间质纤维化过程中肾小管上皮细胞是否发生EMT并阐明相关机制。本课题研究成果有望为DN肾纤维化的临床治疗提供新的治疗靶点。

Diabetic nephropathy（DN）is the most common complication of diabetes and is also one of the leading cause of end-stage renal disease worldwide. Many previous studies have suggested that EMT participated in the development and progression of renal fibrosis during DN in humans and animals. At present, the existence of EMT in renal fibrosis remains the subject of controversial debates, due to the lack of reliable animal models that mimic human DN. Recently, we found that E-cadherin expression was significantly increased in the diabetic monkeys with normal hypertension, but it was significantly decreased in those diabetic monkeys with hypertension compared with the normal monkeys. Based on those work, we hypothesize that systemic hypertension can enhance EMT in renal fibrosis during DN by regulating the expression of many EMT-associated genes. To test the hypothesis, this study will developed a novel drug-induced diabetic hypertensive monkey model, and we will further explore whether tubular epithelial cells undergo EMT during diabetic renal interstitial fibrosis in vivo and in vitro by using the novel DN animal model. Our study may provide a novel therapeutic target for suppressing renal interstitial fibrosis in DN.