Linked Life Data

21636785

Source:http://linkedlifedata.com/resource/pubmed/id/21636785

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2011-6-22
pubmed:abstractText
Adhesion of circulating monocytes to vascular endothelial cells (ECs) is a critical event leading to vascular inflammation and, hence, development of atherosclerosis. MicroRNAs (miRs) are a class of endogenous, highly conserved, noncoding small RNAs that play important roles in regulating gene expression and cellular function, as well as pathogenesis of atherosclerosis. Here, we showed that oscillatory shear stress (OSS) induces the expression of miR-21 at the transcriptional level in cultured human umbilical vein ECs via an increased binding of c-Jun, which is a component of transcription factor activator protein-1 (AP-1), to the promoter region of miR-21. OSS induction of miR-21 inhibited the translation, but not transcription, of peroxisome proliferators-activated receptor-? (PPAR?) by 3'-UTR targeting. Overexpression of miR-21 up-regulated AP-1 activation, which was attenuated by exogenous expression of PPAR?. OSS and overexpression of miR-21 enhanced the expression of adhesion molecules vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and the consequential adhesion of monocytes to ECs. Overexpression of PPAR? significantly attenuated the AP-1-mediated miR-21 expression. These results demonstrate a unique mechanism by which OSS induces AP-1-dependent miR-21 expression, which directly targets PPAR? to inhibit its expression, thereby allowing activation of AP-1 and the promotion of monocyte adhesion. Our findings suggest the presence of a positive feedback loop that enables the sustained induction of miR-21, thus contributing to the proinflammatory responses of vascular endothelium under OSS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10355-60
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
MicroRNA-21 targets peroxisome proliferators-activated receptor-alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation.
pubmed:affiliation
Department of Bioengineering and Institute of Engineering in Medicine, University of California at San Diego, La Jolla, CA 92032, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural