Secreted frizzled-related protein 1 augments vascular smooth muscle cell calcification via activating the Wnt/β-catenin/Runx2 axis

Purpose Vascular calcification (VC) is highly prevalent and a significant cardiovascular risk factor in patients with chronic kidney disease (CKD). Secreted frizzled-related protein 1 (SFRP1) is a secreted glycoprotein closely associated with the Wnt/β-catenin pathway which plays a crucial role in bone formation, but its function and mechanism in VC remain unknown. Methods Serum and radial artery tissues were collected from CKD patients with or without VC. The cellular model of VSMCs’ calcification was established under high-phosphate conditions in vitro. Western blot, qRT-PCR, and immunofluorescence were used to detect SFRP1 expression. The function of SFRP1 was identified by transfection with sh-SFRP1 and pCMV3-SFRP1 plasmid. Results Initially, bioinformatics analysis showed that SFRP1 expression was significantly elevated in high-phosphate-stimulated rat VSMCs. Subsequently, we discovered that the expression of SFRP1 was dramatically increased in the calcified arteries of CKD patients. Functionally, when SFRP1 was knocked down, the calcification process and the expression of Runx2 were attenuated. In contrast, SFRP1 overexpression exacerbated the β-GP-induced VSMCs’ calcification. Mechanistically, we confirmed the activation of Wnt/β-catenin signaling in the in vitro calcification model and this activation was inhibited by SFRP1 knockdown. Furthermore, when the Wnt/β-catenin signaling was enhanced with LiCl, the suppressing effect of SFRP1 knockdown on β-GP-induced osteogenic transdifferentiation of VSMCs was reversed, and calcification was promoted. Conclusion We identified that SFRP1 promoted vascular calcification in CKD partly by regulating the Wnt/β-catenin/Runx2 axis, suggesting that SFRP1 may be a potential biomarker and therapeutic target for VC in CKD.