Li Yao1, Yiting Sun2, Wei Sun3, Tian‐Hua Xu1, Cheng Ren1, Xing Fan1, Li Sun1, Linlin Liu1, Jianan Feng1, Jianfei Ma1, Lining Wang1
1Department of Nephrology, The First Hospital of China Medical University, ShenYang, LiaoNing,
2China Medical University, ShenYang, LiaoNing
3Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
Tóm tắt
<b><i>Aims:</i></b> Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. <b><i>Methods:</i></b> Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 m<smlcap>M</smlcap>, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/β-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of β-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectomized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. <b><i>Results:</i></b> High Pi induced VSMC calcification, downregulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/β-catenin pathway and β-catenin activity. β-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that β-catenin transcriptionally regulated <i>Pit1</i>, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that β-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of β-catenin in the rat model was investigated, we found that aortic calcification was reduced. <b><i>Conclusion:</i></b> These results suggest that β-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.
