Deng Dai, Diao Zongli, Han Xue, Liu Wenhu
Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing, 100050, China.
Calcif Tissue Int. 2016 Jul;99(1):66-75. doi: 10.1007/s00223-016-0117-7. Epub 2016 Feb 19.
Vascular calcification (VC) is highly prevalent and represents a major cardiovascular risk factor in chronic kidney disease (CKD) patients. High phosphate (HP) levels are strongly associated with VC in this population. Secreted frizzled-related protein 5 (SFRP5), one of the inhibitors of the Wnt pathway, is a known anti-inflammatory adipokine with a positive effect on metabolic and cardiovascular diseases, in addition to its anticancer potency. However, the role of SFRP5 in the pathophysiology of VC is unclear. This work aimed to study the mechanism of action of SFRP5 on the progression of HP-induced VC, which resembles the CKD-related VC, through its direct effect on vascular smooth muscle cells (VSMCs) in vitro. Addition of SFRP5 significantly inhibited HP-induced calcification of VSMCs as determined by Alizarin red staining and calcium content. The inhibitory effect of SFRP5 on calcification of VSMCs was due to the suppression of HP-induced expression of calcification and osteoblastic markers. In addition, SFRP5 abrogated HP-induced activation of the Wnt/ß-catenin pathway, which plays a key role in the pathogenesis of VC. The specificity of SFRP5 for the inhibition of calcification of VSMCs was confirmed by using a neutralizing antibody to SFRP5. Our results suggest that SFRP5 inhibits HP-induced calcification of VSMCs by inhibiting the expression of calcification and osteoblastic markers, as well as the Wnt/ß-catenin pathway. Our study may indicate that SFRP5 is a potential therapeutic agent in calcification of VSMCs.
血管钙化（VC）非常普遍，是慢性肾脏病（CKD）患者的主要心血管危险因素。高磷（HP）水平与该人群的VC密切相关。分泌型卷曲相关蛋白5（SFRP5）是Wnt通路的抑制剂之一，是一种已知的抗炎脂肪因子，除了具有抗癌作用外，对代谢和心血管疾病也有积极影响。然而，SFRP5在VC病理生理学中的作用尚不清楚。这项研究旨在通过体外直接作用于血管平滑肌细胞（VSMC），研究SFRP5对HP诱导的VC进展的作用机制，这种VC类似于CKD相关的VC。茜素红染色和钙含量测定结果显示，添加SFRP5可显著抑制HP诱导的VSMC钙化。SFRP5对VSMC钙化的抑制作用是由于其抑制了HP诱导的钙化和成骨标志物的表达。此外，SFRP5消除了HP诱导的Wnt/β-连环蛋白通路的激活，该通路在VC发病机制中起关键作用。使用SFRP5中和抗体证实了SFRP5对VSMC钙化抑制作用的特异性。我们的研究结果表明，SFRP5通过抑制钙化和成骨标志物的表达以及Wnt/β-连环蛋白通路，抑制HP诱导的VSMC钙化。我们的研究可能表明SFRP5是VSMC钙化的潜在治疗药物。
