miR-18a-5p MicroRNA Increases Vascular Smooth Muscle Cell Differentiation by Downregulating Syndecan4
Korean Circulation Journal
;
: 255-263, 2014.
Article
in English
| WPRIM
| ID: wpr-62391
ABSTRACT
BACKGROUND AND OBJECTIVES:
Differentiation and de-differentiation of vascular smooth muscle cells (VSMCs) are important events in atherosclerosis and restenosis after angioplasty. MicroRNAs are considered a key regulator in cellular processes such as differentiation, proliferation, and apoptosis. Here, we report the role of new miR-18a-5p microRNA and its downstream target genes in VSMCs and in a carotid balloon injury model. MATERIALS ANDMETHODS:
Expression of miR-18a-5p and its candidate genes was examined in VSMCs and in a carotid artery injury model by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and microRNA microarray analysis. VSMC differentiation marker genes including smooth muscle (SM) alpha-actin and SM22alpha were determined by Western blot, qRT-PCR, and a SM22alpha promoter study. Gene overexpression or knockdown was performed in VSMCs.RESULTS:
miR-18a-5p was upregulated in the rat carotid artery at the early time after balloon injury. Transfection of the miR-18a-5p mimic promoted the VSMC differentiation markers SM alpha-actin and SM22alpha. In addition, miR-18a-5p expression was induced in differentiated VSMCs, whereas it decreased in de-differentiated VSMCs. We identified syndecan4 as a downstream target of miR-18-5p in VSMCs. Overexpression of syndecan4 decreased Smad2 expression, whereas knockdown of syndecan4 increased Smad2 expression in VSMCs. Finally, we showed that Smad2 induced the expression of VSMC differentiation marker genes in VSMCs.CONCLUSION:
These results indicate that miR-18a-5p is involved in VSMC differentiation by targeting syndecan4.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transfection
/
Carotid Arteries
/
Antigens, Differentiation
/
Cell Differentiation
/
Blotting, Western
/
Polymerase Chain Reaction
/
Actins
/
Apoptosis
/
Angioplasty
/
Carotid Artery Injuries
Limits:
Animals
Language:
English
Journal:
Korean Circulation Journal
Year:
2014
Type:
Article
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