Back to Search
Start Over
miR-27a-3p Targets ATF3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells
- Source :
- Molecular Therapy: Nucleic Acids, Vol 22, Iss, Pp 627-639 (2020), Molecular Therapy. Nucleic Acids
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Vascular calcification, the ectopic deposition of calcium in blood vessels, develops in association with various metabolic diseases and atherosclerosis and is an independent predictor of morbidity and mortality associated with these diseases. Herein, we report that reduction of microRNA-27a-3p (miR-27a-3p) causes an increase in activating transcription factor 3 (ATF3), a novel osteogenic transcription factor, in vascular smooth muscle cells. Both microRNA (miRNA) and mRNA microarrays were performed with rat vascular smooth muscle cells, and reciprocally regulated pairs of miRNA and mRNA were selected after bioinformatics analysis. Inorganic phosphate significantly reduced the expression of miR-27a-3p in A10 cells. The transcript level was also reduced in vitamin D3-administered mouse aortas. miR-27a-3p mimic reduced calcium deposition, whereas miR-27a-3p inhibitor increased it. The Atf3 mRNA level was upregulated in a cellular vascular calcification model, and miR-27a-3p reduced the Atf3 mRNA and protein levels. Transfection with Atf3 could recover the miR-27a-3p-induced reduction of calcium deposition. Our results suggest that reduction of miR-27a-3p may contribute to the development of vascular calcification by de-repression of ATF3.<br />Graphical Abstract<br />Vascular calcification causes stiffness of blood vessels, which causes secondary damage to the cardiovascular system. A reduction in the microRNA miR-27a-3p leads to an increase in the transcription factor ATF3, which induces calcium deposition. This miR-27a-3p/ATF signaling pathway may provide a novel therapeutic target for vascular calcification.
- Subjects :
- 0301 basic medicine
Vascular smooth muscle
Activating transcription factor
chemistry.chemical_element
Calcium
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Drug Discovery
microRNA
vascular smooth muscle cells
Transcription factor
miRNA
ATF3
Chemistry
lcsh:RM1-950
Transfection
Cell biology
030104 developmental biology
lcsh:Therapeutics. Pharmacology
vascular calcification
030220 oncology & carcinogenesis
Molecular Medicine
Original Article
activating transcription factor 3
miR-27a-3p
Subjects
Details
- Language :
- English
- ISSN :
- 21622531
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy: Nucleic Acids
- Accession number :
- edsair.doi.dedup.....e74f5b561f58f8c1c50bac0645a46c12