Lipid metabolism is closely related to the improvement of vascular calcification (VC) in chronic kidney disease (CKD). Globular adiponectin (gAd) has been reported to be involved in the development of VC in CKD, but the detailed regulatory role remains unclear. The present study is aimed to investigate the biological function and the underlying regulation mechanism of gAd in the process of VC during CKD. Vascular smooth muscle cells (VSMCs) calcification was determined by Alizarin Red S staining. Protein signaling related with VC was tested by western blotting. The expression and intracellular localization of runt-related transcription factor 2 (Runx2) was detected by immunofluorescence and uraemic rat with VC was established by a two-step nephrectomy. Combined with the results of Alizarin Red S staining, we discovered that β-glycerophosphate (β-Gp)-induced the osteoblastic differentiation of VSMCs was significantly reversed by gAd treatment. Along with the VSMCs calcification and the increase of Runx2 in β-Gp-exposed VSMCs, the activities of protein kinase B (AKT) and Wnt/β-catenin pathway were enhanced, but that were counteracted by the exposure of gAd in rat and human VSMCs. After administration with agonists of the Wnt (SKL2001) and AKT (SC79), there appeared more osteoblastic differentiation and higher expression of Runx2 in gAd-treated VSMCs, but showing lower impact in the presence of SC79 than that in the presence of SKL2001. In the in vivo experiments, intravenous injection of gAd also significantly inhibited VC and Runx2 level in uraemic rat in a dose-dependent manner, possibly through regulating Wnt/β-catenin pathway. This study demonstrates that gAd ameliorates osteoblastic differentiation of VSMCs possibly by blocking PI3K/AKT and Wnt/β-catenin signaling transduction. The findings provide an important foundation for gAd in treating VC in kidney diseases.

脂质代谢与慢性肾脏病（CKD）血管钙化（VC）的改善密切相关。据报道，球状脂联素（gAd）参与 CKD 中 VC 的发展，但详细的调节作用仍不清楚。本研究旨在探讨gAd在CKD过程中VC的生物学功能及其潜在调控机制。通过茜素红 S 染色测定血管平滑肌细胞 (VSMC) 钙化。通过蛋白质印迹法测试与 VC 相关的蛋白质信号传导。采用免疫荧光法检测runt相关转录因子2（Runx2）的表达和细胞内定位，并通过两步肾切除术建立尿毒症大鼠VC。结合茜素红S染色结果，我们发现gAd处理显着逆转了β-甘油磷酸（β-Gp）诱导的VSMCs成骨细胞分化。在大鼠和人类中，随着 VSMC 钙化和 β-Gp 暴露的 VSMC 中 Runx2 的增加，蛋白激酶 B (AKT) 和 Wnt/β-catenin 通路的活性增强，但受到 gAd 暴露的抵消VSMC。给予Wnt (SKL2001)和AKT (SC79)激动剂后，gAd处理的VSMC中出现更多的成骨细胞分化和更高的Runx2表达，但在SC79存在下的影响低于SKL2001存在下的影响。在体内实验中，静脉注射gAd也以剂量依赖的方式显着抑制尿毒症大鼠VC和Runx2水平，可能是通过调节Wnt/β-catenin通路而实现的。 这项研究表明，gAd 可能通过阻断 PI3K/AKT 和 Wnt/β-catenin 信号转导来改善 VSMC 的成骨细胞分化。该研究结果为 gAd 治疗肾脏疾病 VC 提供了重要基础。