decided to examine changes of miR-126, miR-143, mi-R145, miR-222 and miR-223 expression, known as cardiovascular-related miRNA's, and their target ...
Nephrology Dialysis Transplantation 30 (Supplement 3): iii472–iii489, 2015 doi:10.1093/ndt/gfv191.8
CHRONIC KIDNEY DISEASE. PATHOPHYSIOLOGY, PROGRESSION & RISK FACTORS - 2 SP288
SEVELAMER TREATMENT MODULATES MICRORNA'S EXPRESSION IN AORTA OF MICE WITH CHRONIC KIDNEY DISEASE
Tanja Celic1, Valerie Metzinger-Le Meuth1, Isabelle Six1, Eleonore M'Baya-Moutoula1, Cedric Boudot1, Tilman B Drueke1, Ziad Massy1 and Laurent Metzinger1 1 INSERM U1088, CURS, Amiens, France Introduction and Aims: Chronic kidney disease (CKD) is associated with vascular calcifications and atherosclerosis. Hyperphosphatemia is major contributor to vascular calcification. The phosphate binder, sevelamer, has been shown to prevent vascular abnormalities in CKD experimental and clinical conditions by phosphate dependent and independent effects. MicroRNA's are a class of small non-coding RNAs which are regulators of gene expression. In recent years several microRNAs involved in vascular function have also been linked to CKD-associated cardiovascular disease. We therefore decided to examine changes of miR-126, miR-143, mi-R145, miR-222 and miR-223
expression, known as cardiovascular-related miRNA's, and their target genes in aortas of CKD and non-CKD wild type mice and CKD mice treated with sevelamer-HCl. Methods: All experiments were performed in female C57BL/6J mice, in accord with the principles of the Directive 2010/63/EU of the European Parliament. We used a CKD model which included cortical electrocautery of the right kidney and 2 weeks later left total nephrectomy. Sevelamer treatment was started 2 weeks after CKD induction and continued for 8 weeks. After sacrifice, thoracic aorta was removed for total RNA isolation and RT-qPCR analysis. U6, a non-coding small nuclear RNA, was used as endogenous control. In parallel RT-qPCR was used to quantify vascular protein targets myocardin (MYO), Nuclear Factor I-A (NFI-A) and Glucose Transporter type 4 (GLUT-4). All measurements were performed at 3 times. Results: CKD-associated vascular damage led to down-regulation of aortic miR-143, miR-145 and miR-222 expression, and up-regulation of miR-126 and miR-223 expression. miR-126 levels decreased 1.8 and 2.0 times, and miR-223 levels 3.6 and 3.9 times, respectively, in sevelamer CKD and sevelamer sham groups vs. control CKD group. miR-143 expression increased in sevelamer CKD and sevelamer sham groups vs. control CKD group 0.6 and 1.1 times, and mi-R145 1.5 and 1.8 times, respectively. Analysis of miR-222 expression showed that, again, sevelamer treatment reduced miR-222 increase in treated mice, both sham and CKD 0.8 and 1.1 times respectively as compared to placebo-treated mice. No differences were noted between sevelamer CKD and sevelamer sham groups vs control sham for any miRNA examined. Conclusions: In conclusion, we provide evidence that sevelamer is able to correct CKD-associated anomalies of vascular microRNA expression. Our findings are in support of a direct link between abnormal microRNA expression and uremic vascular toxicity.
© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
