慢性肾脏病矿物质与骨骼异常（CKD-MBD）是危害人类健康的重大慢性疾病。患者晚期出现血管软组织钙化，骨质病变等并发症，死亡率极高。Klotho是最近发现的抗衰老基因，在肾脏小管上皮细胞特异性高表达，而在CKD-MBD早期患者肾组织，血液，尿液中水平下降，是CKD-MBD的重要生物标记物。过氧化物酶体增殖物活化受体γ（PPARγ）能够被乙酰化修饰并增强对Klotho的转录上调功能。我们在前期工作的基础上提出PPARγ乙酰化上调Klotho缓解CKD-MBD损害的新假说，从PPARγ乙酰化调控保护CKD-MBD模型小鼠病理改变， PPAR-γ乙酰化修饰机理，及对靶基因Klotho的上调作用三个方面探讨PPARγ乙酰化干预缓解CKD-MBD的有效性和作用机理，为设计以Klotho为靶点的CKD-MBD新治疗措施提供分子生物学依据。

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is one of major threats to global public health. CKD-MBD patients at late stage show extensive cardiovascular cal-cification and osteosposis with very high mortality. Klotho is a recently discovered an-ti-aging gene highly expressed in the kidney tubule epithelial cells. CKD-MBD patients display decreased Klotho expression early in Kidney as well as reduced Klotho in blood and urine, suggesting that Klotho is an important biomarker of CKD-MBD. Peroxisome proliferator -activated receptor γ (PPARγ) is a nuclear membrane-bound hormone recep-tor/transcription factor that can be acetylated and directly regulates Klotho transcription. Based on our preliminary data, we hypothesized that PPARγ acetylation up-regulates Klotho and alleviates CKD-MBD pathogenesis. We propose in this project to evaluate the efficacy of PPARγ acetylation on the protection of CKD-MBD animal models, to examine the mode of PPARγ acetylation modification, and to study PPARγ acetylation regulation of Klotho transcription. The study will demonstrate the effectiveness of PPARγ acetylation and Klotho regulation on CKD-MBD therapy and elucidate its underlining mechanism.