临床研究发现运动可改善慢性肾脏病（CKD）患者的预后，但具体机制尚未清楚。研究发现小鼠骨骼肌特异性过表达PGC-1α（mckPGC-1α）可模拟持续运动状态。我们的预实验发现mckPGC-1α可改善叶酸性肾病小鼠模型（FAN）的肾脏纤维化和线粒体损伤。mckPGC-1α能刺激多种肌肉因子（myokines）分泌，其中Irisin有类似保护肾脏的作用，提示骨骼肌运动产生的Irisin可能介导了肌肉对肾脏的远程调控。因此本项目将采用mckPGC-1α小鼠，结合FAN肾损伤小鼠模型，采用分子生物学、代谢组学及Seahorse能量代谢实时测定等方法阐明Irisin是介导mckPGC-1α改善肾脏损伤的重要肌肉因子，其作用机制可能是通过抑制TGF-β1-SMAD2/3通路改善肾小管上皮细胞的能量代谢。我们的研究将有助于解释运动通过肌肉对肾脏的调控，为临床采用肌肉因子或运动疗法防治CKD提供理论依据。

Clinical studies have suggested that exercises can improve the prognosis of chronic kidney disease (CKD), however, the underlying mechanism remains unknown. Muscle specific over-expressing PGC-1α (mckPGC-1α) mouse could mimic persistent exercises situation. In our previous study, the kidney injury and fibrosis-related gene expression profile in folic acid-induced nephropathy (FAN) were ameliorated in mckPGC-1α mice. As Irisin, a muscle-secreted myokine, exhibited similar effects in the study, we hypothesize that Irisin induced by exercises mediates the muscle-kidney communication. In this study, we plan to make mckPGC-1α mice and wild type mice FAN models. By using molecular biology methods, cell biology methods, metabolomics and real-time detection of energy metabolism, etc., we want to demonstrate that Irisin is the major myokine to mediate the renoprotective effect in mckPGC-1α mice. The involved mechanism could be that Irisin antagonizes TGF-β1-Smad2/3 signaling pathway to aggravate tubular metabolism reprogramming and renal fibrosis. Our study will help to understand how exercise protects kidney though muscle-kidney communication. It will provide theoretic evidence to treat CKD with exercise or Irisin.