title: Secreted Frizzled-Related Protein 5 Attenuates High Phosphate-Induced Calcification in Vascular Smooth Muscle Cells by Inhibiting the Wnt/ß-Catenin Pathway.
abstract: 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.
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing, 100050, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Deng
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing, 100050, China.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Diao
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing, 100050, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing, 100050, China. liuwenhu2013@163.com.
authors.forename: Wenhu
authors.initials: W
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology*; D012307:Risk Factors; D061205:Vascular Calcification / Q000139:chemically induced / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; D008565:Membrane Proteins; D010710:Phosphates; D051176:beta Catenin; C495270:CTNNB1 protein, human; C118511:SFRP5 protein, human; D000094742:Secreted Frizzled-Related Proteins
keywords: Chronic kidney disease; Secreted frizzled-related protein 5; Vascular calcification; Wnt/ß-catenin pathway