MicroRNA-223-3p inhibits vascular calcification and the osteogenic switch of vascular smooth muscle cells

• Authors: Yingchun Han, Capital Medical University; Jichao Zhang, Capital Medical University; Shan Huang, Capital Medical University; Naixuan Cheng, Capital Medical University; Congcong Zhang, Capital Medical University; Yulin Li, Capital Medical University; Xiaonan Wang, Emory University; Jinghua Liu, Capital Medical University; Bin You, Capital Medical University; Jie Du, Capital Medical University
• Journal Title: Journal of Biological Chemistry
• Volume: Volume 296
• Publisher: American Society for Biochemistry and Molecular Biology | 2021-01-01, Pages 100483-100483
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.jbc.2021.100483
• Subjects: Chemistry, Biochemistry; Biology, Molecular; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Chronic kidney disease; Arterial; MIR-223; Osteoclastogenesis; Deficiency; Roles

Abstract

Vascular calcification is the ectopic deposition of calcium hydroxyapatite minerals in arterial wall, which involves the transdifferentiation of vascular smooth muscle cells (VSMCs) toward an osteogenic phenotype. However, the underlying molecular mechanisms regulating the VSMC osteogenic switch remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in vascular calcification. miRNA-seq transcriptome analysis identified miR-223-3p as a candidate miRNA in calcified mouse aortas. MiR-223-3p knockout aggravated calcification in both medial and atherosclerotic vascular calcification models. Further, RNA-seq transcriptome analysis verified JAK-STAT and PPAR signaling pathways were upregulated in both medial and atherosclerotic calcified aortas. Overlapping genes in these signaling pathways with predicted target genes of miR-223-3p derived from miRNA databases, we identified signal transducer and activator of transcription 3 (STAT3) as a potential target gene of miR-223-3p in vascular calcification. In vitro experiments showed that miR-223-3p blocked interleukin-6 (IL-6)/STAT3 signaling, thereby preventing the osteogenic switch and calcification of VSMCs. In contrast, overexpression of STAT3 diminished the effect of miR-223-3p. Taken together, the results indicate a protective role of miR-223-3p that inhibits both medial and atherosclerotic vascular calcification by regulating IL-6/STAT3 signaling-mediated VSMC transdifferentiation.