Background: Patients with chronic kidney disease (CKD) have abnormal calcification in vascular tissue that is a risk factor for cardiovascular disease. However, the specific molecular mechanisms for vascular calcification remain largely unknown. The present study aimed to determine the differentially expressed miRs and the underlying molecular mechanisms of miR-153-3p in vascular calcification induced by adenine.
Methods: Differentially expressed miRs were screened using a microarray chip in the thoracic aorta. miRs and mRNA expression were measured by RT-qPCR. Protein expression was performed by western blotting analysis. Aortic calcification was confirmed by Von Kossa staining. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay.
Results: Our results revealed that the expression of miR-153-3p was significantly down-regulated in the thoracic aorta from adenine-fed rats compared with that of the control group. Transfection of miR-153-3p into the thoracic aorta markedly suppressed adenine-induced aortic calcification and significantly decreased the mRNA expression of ALP, OC, OSX, SOST and Runx2. Further studies indicated that Runx2 was a direct target gene of miR-153-3p, which was verified by dual luciferase reporter assay.
Conclusion: These results suggest that increased vascular miR-153-3p expression attenuates adenine-induced aortic calcification via inhibiting osteogenic trans-differentiation in the thoracic aorta.
Keywords: Runx2; aortic calcification; miR-153-3p; osteogenic trans-differentiation.
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