肾脏纤维化在糖尿病肾病（DN）发生发展过程中作用重要，机制未明。前期研究发现，原癌基因metadherin（MTDH）在DN动物模型和高糖诱导的小鼠来源肾小管上皮细胞（mTEC）上皮-间质转化模型中均高表达，迄今未见相关报道；自主研发治疗DN的中药肾康丸（已获国家发明专利）可抑制高糖诱导的mTEC 中MTDH的表达。推测：1.DN时MTDH通过下游TGF-β、MAPK信号通路介导肾脏纤维化；2.肾康丸通过抑制该通路发挥肾保护作用。本项目拟以MTDH为切入点，应用mTEC为细胞模型、自发性2型DN动物db/db小鼠为动物模型，采用RNA干扰、免疫荧光染色等方法，通过体内、体外实验进一步阐明DN时MTDH通过下游TGF-β、MAPK信号通路介导肾脏纤维化的分子机制，并观察肾康丸对该过程的影响。研究结果有望揭示一条DN肾脏纤维化的新通路，确立一个DN治疗的新靶点，阐明一种肾康丸治疗DN的新机制。

Renal fibrosis is the common end point of diabetic nephropathy(DN), but the mechanism remains unknown. According to previous study, metadherin(MTDH) was found to be highly expressed in DN models of db/db mice and high glucose-induced mTEC, no relevant study has been done to date. ShenKang pill, an independent investigated traditional Chinese medicine targetting DN, can reduce HG-induced MTDH expression in renal epithelial cells(mTEC). Thus,we hypothesis that: 1. MTDH might mediate renal fibrosis in DN via TGF-β/MAPK downstream signaling regulation; 2. ShenKang pill could draw its renoprotective effect by supressing TGF-β/MAPK signal transdution. In this project, MTDH was regarded as the cutting point, using mTECs and db/db mice as models in vitro and in vivo, with RNA interfere, immunofluorescence staining et al technologies, to reveal the mechanism that how MTDH function in TGF-β/MAPK signal pathway in renal fibrosis of DN and the efficacy of ShenKang pill to this process. The findings are expected to reveal a new pathway for DN renal fibrosis, a new target for DN treatment, and a new mechanism for ShenKang pill treatment on DN.