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Sclerostin/Receptor Related Protein 4 and Ginkgo Biloba Extract Alleviates β-Glycerophosphate-Induced Vascular Smooth Muscle Cell Calcification By Inhibiting Wnt/β-Catenin Pathway

Version 3 2024-06-19, 23:20
Version 2 2024-06-03, 02:36
Version 1 2024-01-11, 04:39
journal contribution
posted on 2024-06-19, 23:20 authored by Jian Wang, Xiaobo Qiu, Tianhua Xu, Zitong ShengZitong Sheng, Li Yao
Background: Abnormal mineral metabolism in patients with chronic kidney disease (CKD) may lead to vascular calcification, which is markedly associated with adverse events, including ischemic cardiac diseases and all-cause cardiovascular mortality. Thus, preventing and treating vascular calcification play an important role in improving the prognosis of CKD patients. Objectives: To investigate the potential functions of sclerostin and low-density lipoprotein receptor-related protein 4 (Lrp4) in alleviating the β-glycerophosphate (β-GP)-induced vascular smooth muscle cell (VSMC) calcification, and the protective effect of Ginkgo biloba extract (GBE). Methods: VSMC were extracted from Sprague-Dawley rat aorta and cultured in medium. The VSMCs were divided into 3 groups: (1) Negative control group, (2) β-GP group, in which the VSMCs were treated with β-GP, and (3) GBE and β-GP group, where the VSMCs were treated with both β-GP and GBE. The calcium nodules within the cells were examined by using Alizarin red S staining. The mRNA expression levels of β-catenin and bone gamma-carboxyglutamic-acid-containing proteins (BGP) were detected by real-time PCR. The protein levels of sclerostin and Lrp4 were determined by Western blot. Results: Alizarin red S staining showed that the VSMCs in β-GP group had a distinct orange-red precipitate when compared with VSMCs in the negative control group, while the orange-red precipitate of the GBE and β-GP group was significantly reduced compared to the β-GP group. Real-time PCR showed that the mRNA levels of β-catenin and BGP in VSMCs of β-GP group were significantly higher than those of the negative control group (p < 0.05); while they were significantly reduced in VSMCs of the GBE and β-GP group (p < 0.05). Western blot results showed that the expression of sclerostin in the β-GP group was significantly higher than that in the control group (p < 0.05), whereas Lrp4 was significantly lower than in control group (p < 0.05). Sclerostin in GBE and β-GP group was significantly reduced (p < 0.05), but Lrp4 was significantly elevated when compared with that of the β-GP group (p < 0.05). Conclusion: β-GP induced VSMC calcification by activating the Wnt/β-catenin signaling pathway. Sclerostin and Lrp4 were involved in β-GP-induced VSMC calcification and play an important role. GBE could alleviate VSMC calcification induced by β-GP through inhibiting the Wnt/β-catenin signaling pathway.

History

Journal

Blood Purification

Volume

47

Pagination

17-23

Location

Basel, Switzerland

ISSN

0253-5068

eISSN

1421-9735

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

Suppl. 1

Publisher

Karger Publishers