Effect of Erythropoietin on Calcification of Vascular Smooth Muscle Cells and Its Molecular Regulatory Mechanism
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ORIGINAL ARTICLE
Effect of Erythropoietin on Calcification of Vascular Smooth Muscle Cells and Its Molecular Regulatory Mechanism Xunjia Li 1 & Xushun Jiang 1 & Fang He 1 & Yunfeng Xia 1 & Xuemei Chen 2 & Xiaogang Du 1,3 & Hua Gan 1 Received: 5 August 2020 / Accepted: 19 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract To investigate its effect and molecular regulatory mechanism on vascular calcification, EPO was added to vascular smooth muscle cells cultured in vitro and injected intraperitoneally into SD rats. The effect of EPO on VSMC calcification was determined by alizarin red staining and ALP activity. Differentially expressed genes were screened by transcriptome sequencing and the relationship and function were verified. We found EPO promotes VSMC calcification in vitro and blood calcification in vivo in a dose-dependent manner. A total of 88 upregulated genes and 59 downregulated genes were detected in transcriptome sequencing, among which the expression of genes associated with bone formation exhibited a marked increase, namely the GATA6 transcription factor, BMP2, RUNX2, OPN, and OCN. Dual luciferase assay has indicated that the binding of GATA6 to BMP2 promoter facilitates the transcription of BMP2. Taken together, findings indicate that EPO can enhance the calcification of VSMCs by activating the GATA6/BMP2 signal axis. Keywords EPO . VSMCs . Calcification . GATA6 . BMP2
Abbreviations EPO Erythropoietin VSMCs Vascular smooth muscle cells ALP Alkaline phosphatase ChIP Chromatin immunoprecipitation CKD Chronic kidney disease BMP2 Bone morphogenetic protein-2
Associate Editor Adrian Chester oversaw the review of this article * Hua Gan [email protected] 1
Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400042, China
2
Emergency Department, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400042, China
3
Laboratory of Lipid & Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400042, China
Introduction Chronic kidney disease (CKD) significantly increases the incidence and mortality of cardiovascular incidents, especially in patients relying on dialysis treatment [1, 2]. Vascular calcification is widely seen in CKD patients and aggravates the evolution of CKD. The morbidity and mortality of cardiovascular diseases rise with the aggravation of vascular calcification. Some research indicates that the vascular calcification score can predict all-cause mortality and cardiovascular mortality of CKD patients, suggesting vascular calcification functions as one of the pivotal factors of high cardiovascular incidence in patients with CKD [3, 4]. The risk of cardiovascular disease in CKD patients with calcification was 1.23–2.70 times higher than those without calcification in the abdominal aorta [5–8]. Vascular calcification is currently believed to develop when complex pathophysiologic changes occur in the whole
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