肾脏纤维化是慢性肾脏病（CKD）进展至终末期肾脏病（ESRD）的共同通路。肾小管上皮细胞-间充质转分化（EMT）是肾脏纤维化发生发展的重要机制，受众多细胞因子的调控。其中TGFβ/Smads通路是公认的主要途径。Apelin与其受体APJ广泛分布于人体组织器官中。现已证实它能促进肝纤维化，抑制心肌纤维化。对于该系统与肾脏纤维化的关系尚缺乏报道。前期研究显示，尿毒症患者血浆Apelin水平显著高于正常人，且Apelin能抑制肾小管EMT。本研究计划采用体外培养人肾小管上皮细胞、单侧输尿管结扎致肾脏纤维化小鼠模型、Apelin基因敲除小鼠模型，通过分子生物学和免疫组织化学等技术，从多层面探讨CKD状态下Apelin/APJ系统的代偿性变化，以及Apelin能否通过抑制经典的TGFβ/Smads途径抑制肾小管EMT，进而减轻肾脏纤维化，延缓CKD进展。

Renal fibrosis is the final common pathway that chronic kidney disease (CKD) progresses to end-stage renal diease (ESRD). Renal tubular epithelial mesenchymal transition (EMT) is the important mechanism of renal fibrosis, which is regulated by much cytokine. The TGFβ/Smads signaling pathway is accepted as the main one to induce renal fibrosis. As an endogenous peptide, apelin and its receptor APJ is widely distributed in most tissues. It has been proved that apelin/APJ system promotes hepatic pibrosis, but can play a certain protective effect in myocardial fibrosis. However, there is still lack of reports about the relationship between apelin/APJ system and renal fibrosis. Our previous study showed that the serum level of apelin in uremia patients was much higher than healthy controls. We also observed that apelin was able to inhibit TGFβ1-induced EMT of tubular epithelial cells. In the present study, we will culture human renal tubular epithelial cells, build renal interstitial fibrosis mouse model and apelin deficient mouse model, to investigate the relationship between apelin/APJ system and renal fibrosis from multi-angle. We want to clarify that the apelin/APJ system can suppress renal fibrosis and CKD progression through the important TGFβ/Smads pathway, which would make apelin be deeply researched as a potential medicine for CKD in future.