MicoroRNA-297a regulates vascular calcification by targeting fibroblast growth factor 23

Abstract

Objective Vascular calcification is one of the major characteristics in patients with various types of chronic inflammatory disorders. miRNAs have been shown to be involved in many normal biological functions as well as diseases, however, their role in vascular calcification has not received much attention. Methods In the current study, we built vascular calcification rat model using vitamin D3 plus nicotine and analyzed miRNA expression profile by miRNA chip assay. Potential target of one selected miRNA with sharpest variation in expression was predicted by both PicTar and TargetScan. The impact of the selected miRNA on the expression of the potential target on both mRNA and protein levels was measured by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting, respectively. Results The mmu-miR-297a was selected as the focus of the study on the early construction of stable angiocalcified animal models; As the target gene of mmu-miR-297a, fibroblast growth factor 23 (FGF23) plays an important role in regulating vascular growth; The results of Real-time PCR showed that the expression of mmu-miR-297a was significantly reduced in the model group; Real time PCR also found that FGF23 was up-regulated in the aortic tissue of the model group, while Klotho was significantly reduced (P=0.000); The expression of Western blotting analysis protein level FGF23 and Klotho was consistent with the mRNA level results, FGF23 was up-regulated in the model group, and Klotho was significantly reduced. Conclusion Our results indicated that FGF23 was target of miR-297a and decreased miR-297a in vascular calcification lead to the increase of FGF23, which together with Klotho might enhance vascular calcification. The findings of this study could provide valuable information for the understanding of mechanisms underlying miR-dependent vascular calcification as well as potential treatment target for the disease. Key words: MicroRNAs; MicroRNA-297a; Vascular calcification; Fibroblast growth factor 23