Sclerostin is involved in osteogenic transdifferentiation of vascular smooth muscle cells in chronic kidney disease-associated vascular calcification with non-canonical Wnt signaling

Qiong Xiao; Yun Tang; Haojun Luo; Sipei Chen; Rong Chen; Zhe Yan; Lei Pu; Li Wang; Guisen Li; Yi Li

doi:10.1080/0886022X.2022.2114370

Renal Failure (Dec 2022)

Sclerostin is involved in osteogenic transdifferentiation of vascular smooth muscle cells in chronic kidney disease-associated vascular calcification with non-canonical Wnt signaling

Qiong Xiao,
Yun Tang,
Haojun Luo,
Sipei Chen,
Rong Chen,
Zhe Yan,
Lei Pu,
Li Wang,
Guisen Li,
Yi Li

Affiliations

Qiong Xiao: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Yun Tang: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Haojun Luo: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Sipei Chen: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Rong Chen: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Zhe Yan: College of Integration of Traditional Chinese and Western Medicine, Southwest Medical University, Luzhou, PR China
Lei Pu: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Li Wang: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Guisen Li: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China
Yi Li: Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, PR China

DOI: https://doi.org/10.1080/0886022X.2022.2114370
Journal volume & issue: Vol. 44, no. 1
pp. 1426 – 1442

Abstract

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Vascular calcification is prominent in patients with chronic kidney disease (CKD) and is a strong predictor of cardiovascular mortality in the CKD population. However, the mechanism underlying CKD-associated vascular calcification remains unclear. To identify potential therapeutic targets, a 5/6 nephrectomy rat model was established by feeding of a high-phosphorous diet as the CKD group and compared with sham group rats at 4 and 16 weeks. Sequencing analyses of the rat aorta revealed 643 upregulated and 1023 downregulated genes at 4 weeks, as well as 899 upregulated and 1185 downregulated genes at 16 weeks in the CKD group compared to the sham group. Bioinformatics analyses suggested that SOST (which encodes sclerostin) and Wnt signaling are involved in CKD-associated vascular calcification. Furthermore, protein-protein interactions analysis revealed interactions between SOST, WNT5A, and WNT5B, that involved runt-related transcription factor 2 (RUNX2) and transgelin (TAGLN). SOST was increased in CKD-associated vascular calcification following reduction of the Wnt signaling, including WNT5A and WNT5B, both in vivo and in vitro. TargetScan was used to predict the microRNAs (miRNAs) targeting WNT5A and WNT5B. The expression levels of miR-542-3p, miR-298-3p, miR-376b-5p, and miR-3568 were significantly reduced, whereas that of miR-742-3p was significantly increased in calcified rat aortic vascular smooth muscle cells (VSMCs). In CKD rat aortas, the expression of miR-542-3p, miR-298-3p, miR-376b-5p, miR-3568, miR-742-3p, and miR-22-5p were significantly reduced at both 4 and 16 weeks. Altogether, owing to several assessments, potentially diagnostic and prognostic biomarkers for improving common CKD diagnostic tools were identified in this study. Abbreviations: BUN: blood urea nitrogen; CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral bone disorder; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GO: the Gene Ontology; HE: hematoxylin-eosin; HRP: horseradish peroxidase; KEGG: Kyoto Encyclopedia of Genes and Genomes; MiRNAs: microRNAs; PAS: periodic acid-Schiff; RUNX2: runt-related transcription factor 2; SCr: serum creatinine; STRING: the Search Tool for the Retrieval of Interacting Genes/Proteins; TAGLN: transgelin; VSMC: vascular smooth muscle cell.

Published in Renal Failure

ISSN: 0886-022X (Print); 1525-6049 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the genitourinary system. Urology
Website: https://www.tandfonline.com/journals/irnf

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