MicroRNA-۲۹۷a regulates vascular calcification by targeting fibroblast growth factor ۲۳

Objective(s): Vascular calcification is one 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. Materials and Methods: In the current study, we built a vascular calcification rat model using vitamin D۳ plus nicotine and analyzed miRNA expression profile by miRNA chip assay. Potential target of one selected miRNA with sharpest variation in expression were 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 were measured by RT-PCR and Western blot, respectively. Results: Our results identified ۱۶ dysregulated miRNAs, among which miR-۲۹۷a showed the sharpest variation. Further analysis focusing on miR-۲۹۷a revealed that fibroblast growth factor ۲۳ (FGF۲۳) was a potential target of miR۲۹۷a. Measurement of FGF۲۳ and its regulator Klotho on both mRNA and protein levels demonstrated that FGF۲۳ was significantly increased while Klotho was decreased in rats with vascular calcification. Conclusion: Our results indicated that FGF۲۳ was target of miR-۲۹۷a and decreased miR-۲۹۷a in vascular calcification lead to the increase of FGF۲۳, 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.

کلیدواژه ها:

Fibroblast growth factor ۲۳ ، MicroRNA-۲۹۷a ، Chronic inflammatory disorder ، Vascular calcification ، Klotho