Abstract
Objective
Osteopontin (OPN) is a multifunctional protein found in abundance in atherosclerotic
plaques. Angiotensin II (Ang II) promotes atherosclerosis by inducing adhesion and
migration of vascular smooth muscle cells (VSMCs). MicroRNAs (miRNAs) are critical
regulators of protein expression. However, the relationship between Ang II, miRNAs
and OPN has yet to be fully explored.
Methods and results
Using cultured VSMCs, we found that Ang II increased cellular OPN protein expression
4 h after treatment by 420 ± 54% (p < 0.03) in a translation dependent manner. Sequence analysis revealed a putative
binding site for mir181a and raised the possibility that miR181a is a potential regulatory
mechanism for OPN expression. We demonstrated that Ang II decreased miR181a expression
by 52 ± 7% (p < 0 .0001) and overexpressing miR181a inhibited Ang II induced increases in OPN protein
expression by 69 ± 9% (p < 0.05). Furthermore, we demonstrated that miR181a is functionally important in that
overexpression of miR181a inhibited VSMCs adhesion to collagen in response to Ang
II as compared to controls by 36 ± 4%. (p < 0.05)
Conclusions
These results demonstrate that miR181a regulates OPN expression and that altering
miR181a expression may be a novel therapeutic approach to modulate OPN protein expression.
Highlights
- Ang II increases OPN expression in a translation dependent manner in VSMCs.
- Ang II decreases mir181a expression in VSMCs.
- Overexpression of mir181a inhibits Ang II induced OPN expression in VSMCs.
- OPN is essential for adhesion of VSMCs to collagen substrates.
- Overexpression of mir181a decreases adhesion of VSMCs to collagen substrates.
Keywords
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Article info
Publication history
Published online: March 04, 2013
Accepted:
January 21,
2013
Received in revised form:
January 2,
2013
Received:
June 19,
2012
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.