SFRP1 Inhibits Vascular Smooth Muscle Cell Calcification Via the Wnt/β-catenin Signaling Pathway

LUO Wenjun; LIU Canzhao; WANG Xianbao

doi:10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2025.0511

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SFRP1 Inhibits Vascular Smooth Muscle Cell Calcification Via the Wnt/β-catenin Signaling Pathway

Preclinic Research | 更新时间：2025-12-04

- SFRP1 Inhibits Vascular Smooth Muscle Cell Calcification Via the Wnt/β-catenin Signaling Pathway
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 46, Issue 5, Pages: 816-825(2025)
- 作者机构：
  
  1.南方医科大学珠江医院心脏中心实验室心血管内科，广东广州 510280
  2.南方医科大学珠江医院转化医学研究中心，广东广州 510280
- 作者简介：
  
  WANG Xianbao； E-mail： wxb2007wxb@126.com
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2025.0511
  CLC： R543
- Received：26 June 2025，
  
  Revised：2025-08-04，
  
  Accepted：17 August 2025，
  
  Published：20 September 2025
- 稿件说明：
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罗文君,刘灿昭,王先宝.分泌型卷曲相关蛋白1通过Wnt/β-catenin通路抑制血管平滑肌细胞钙化[J].中山大学学报（医学科学版）,2025,46(05):816-825.

LUO Wenjun,LIU Canzhao,WANG Xianbao.SFRP1 Inhibits Vascular Smooth Muscle Cell Calcification Via the Wnt/β-catenin Signaling Pathway[J].Journal of Sun Yat-sen University(Medical Sciences),2025,46(05):816-825.
罗文君,刘灿昭,王先宝.分泌型卷曲相关蛋白1通过Wnt/β-catenin通路抑制血管平滑肌细胞钙化[J].中山大学学报（医学科学版）,2025,46(05):816-825. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2025.0511.

LUO Wenjun,LIU Canzhao,WANG Xianbao.SFRP1 Inhibits Vascular Smooth Muscle Cell Calcification Via the Wnt/β-catenin Signaling Pathway[J].Journal of Sun Yat-sen University(Medical Sciences),2025,46(05):816-825. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2025.0511.

摘要

目的

探讨分泌型卷曲相关蛋白1（SFRP1）通过Wnt/β-catenin通路对血管平滑肌细胞成骨分化的影响。

方法

使用原代人主动脉血管平滑肌细胞，转染SFRP1小干扰RNA（siSFRP1）敲低SFRP1在人血管平滑肌细胞表达，转染慢病毒Lenti-Sfrp1过表达SFRP1，使用3 mmol/L的磷酸二氢钠（Pi）刺激构建细胞血管钙化模型。体内实验采用维生素D

（VD

）构建急性血管钙化模型，腹腔注射SFRP1抑制剂WAY316606（0.5 mg/kg，7 d），Micro-CT检测小鼠主动脉钙化程度。Western blot检测成骨分化指标RUNX2、BMP2，血管平滑肌细胞收缩标志SM22α，Wnt信号通路β-catenin蛋白水平表达。钙含量检测与茜素红染色评估血管钙化严重程度，研究SFRP1对血管平滑肌钙化的影响。

结果

在原代人血管平滑肌细胞钙化模型与急性血管钙化模型中，SFRP1蛋白水平表达明显下调（0.30

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.02，

=0.02；0.15

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.03，

=0.04）。使用小分子干扰RNA敲低SFRP1，明显上调RUNX2表达（2.91

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.38，

＜0.05），下调SM22α表达（0.48

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.08，

＜0.05），同时激活Wnt/β-catenin信号通路（2.01

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.11，

=0.003）。体内实验使用SFRP1抑制剂加重小鼠主动脉钙化，上调BMP2与β-catenin表达（3.11

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.55，

=0.04；3.97

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.44，

=0.03）。使用慢病毒过表达SFRP1，明显下调RUNX2（1.34

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.04，

=0.02）与β-catenin表达（1.06

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.06，

=0.04），上调SM22α表达（0.74

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.03，

=0.03）。茜素红染色定量与钙含量检测显示过表达SFRP1抑制血管平滑肌细胞钙化（1.36

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.08，

=0.000 6；1.51

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.03，

=0.002 1）。

结论

SFRP1通过抑制Wnt/β-catenin通路减轻血管平滑肌细胞成骨分化。

Abstract

Objective

To investigate the effect of secreted frizzled related protein 1（SFRP1） via Wnt/β-catenin signaling pathway on calcification of vascular smooth muscle cell.

Methods

Primary human aortic vascular smooth muscle cells were transfected with SFRP1-specific small interfering RNA （siSFRP1） to knock down SFRP1 expression， transfected with lentiviral vector Lenti-Sfrp1 to overexpress SFRP1， and stimulated with 3 mmol/L sodium dihydrogen phosphate （Pi） to establish a cellular vascular calcification model.

In vivo

， a mouse model of acute vascular calcification was established using vitamin D

（VD

） treatment. The SFRP1 inhibitor WAY-316606 was administered intraperitoneally （0.5 mg/kg daily for 7 days）. Aortic calcification was quantified by micro-computed tomography （micro-CT）. Western blot analysis was performed to detect the expression of osteogenic differentiation markers （RUNX2 and BMP2）， vascular smooth muscle cell contractile marker SM22α， and β-catenin protein in the Wnt signaling pathway. The severity of vascular calcification was evaluated through calcium content measurement and Alizarin Red staining. These approaches were employed to investigate the effect of SFRP1 on VSMC calcification.

Results

In the primary human vascular smooth muscle cell calcification model and the acute vascular calcification model， the expression of SFRP1 protein was significantly do

wn-regulated （0.30

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.02，

= 0.02； 0.15

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.03，

= 0.04）. The expression of RUNX2 （2.91

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.38，

＜ 0.05） was significantly up-regulated and SM22α （0.48

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.08，

＜ 0.05） were significantly down-regulated by small interfering RNA （siRNA）， whereas the Wnt/β-catenin signaling pathway was also significantly activated （2.01

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.11，

= 0.003）.

In vivo

， inhibition of SFRP1 exacerbated aortic calcification and significantly up-regulated the expression of BMP2 （3.11

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.55，

= 0.04） and β-catenin （3.97

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.44，

= 0.03）. Lentiviral overexpression of SFRP1 significantly downregulated RUNX2 （1.34

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203152&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203168&type=

1.52400005

0.04，

= 0.02） and β-catenin （1.06

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203152&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203168&type=

1.52400005

0.06，

= 0.04） expression， while upregulating SM22α （0.74

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203152&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203168&type=

1.52400005

0.03，

= 0.03）. Quantitative alizarin red staining and calcium content assays demonstrated that SFRP1 overexpression significantly inhibited vascular smooth muscle cell calcification （1.36

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203151&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203157&type=

1.52400005

0.08，

=0.000 6；1.51

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203158&type=

2.28600001

https://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=95203183&type=

1.52400005

0.03，

=0.002 1）.

Conclusion

SFRP1 attenuates vascular smooth muscle cell calcification via the Wnt/β-catenin signaling pathway.

关键词

Keywords

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Related Institution

Department of Cardiology， Laboratory of Heart Center， Zhujiang Hospital， Southern Medical University

Department of Pathophysiology， Zhongshan School of Medicine， Sun Yat-Sen University

Department of Anesthesiology， The Third Affiliated Hospital， Southern Medical University

Department of Pathology， The First Affiliated Hospital， Sun Yat-sen University

Department of Pathophysiology，Zhongshan Medical School，Sun Yat-Sen University

Postal code：510080
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