Mechanism of Sclerostin/Lrp4 in the regulation of vascular smooth muscle cell calcification
10.3760/cma.j.issn.1001-7097.2018.03.008
- VernacularTitle:Sclerostin/Lrp4调节血管平滑肌细胞钙化的机制研究
- Author:
Jian WANG
1
;
Xiaobo QIU
;
Zitong SHENG
;
Tianhua XU
;
Yinke DU
;
Lining WANG
;
Li YAO
Author Information
1. 中国医科大学附属第一医院肾内科
- Keywords:
Renal insufficiency,chronic;
Calcinosis;
LDL-receptor related proteins;
Sclerostin;
Wnt/β-catenin;
GBE
- From:
Chinese Journal of Nephrology
2018;34(3):208-213
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the possible mechanism of sclerostin/Lrp4 in calcification of VSMC induced by high phosphorus and the protective effect of Ginkgo biloba extract.Methods Aortic vascular smooth muscle cells (VSMCs) of SD rats were extracted and identified.VSMCs were divided into normal control group,high phosphorus induced calcification group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid),and high phosphorus induced calcification+Ginkgo biloba extract intervention group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid+0.5 mg/ml GBE),cultured in different mediums for 14 days.Vonkossa staining and alizarin red staining were used to detect the calcification of VSMCs.The mRNA level of BGP was detected by real time PCR,and the protein expressions of sclerostin and Lrp4 were detected by Western blot.Results Compared with normal control group,vonkossa staining and alizarin red staining showed significant calcium deposition in calcification group.Compared with calcification group,calcium salt deposition was significantly reduced in GBE treatment group.Real time PCR results showed β-catenin and BGP mRNA expressions in VSMC calcification group were higher than those in normal control group (P＜ 0.05).mRNA expressions of β-catenin and BGP in GBE treatment group were lower than those in calcification group (all P ＜ 0.05).Compared with normal control group,the protein expression of sclerostin was increased,but the protein expression of Lrp4 was decreased in calcified group (all P ＜ 0.05).Compared with calcification group,the protein expression of sclerostin decreased and the protein expression of Lrp4 increased in GBE treatment group (all P ＜ 0.05).Conclusions High phosphorus can induce VSMC calcification by activating Wn/β-catenin signaling pathway.Sclerostin/Lrp4 is involved in hyperphosphine-induced VSMC calcification.GBE can reduce the high phosphorus induced VSMC calcification by regulating the Wnt/β-catenin signaling pathway.
