Source:http://linkedlifedata.com/resource/pubmed/id/21109779
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
|
pubmed:dateCreated |
2011-1-4
|
pubmed:abstractText |
MicroRNAs are phenotypic regulators of vascular smooth muscle cells (VSMCs). In this paper, we demonstrate that miR-146a targets the Krüppel-like factor 4 (KLF4) 3'-untranslated region and has an important role in promoting VSMC proliferation in vitro and vascular neointimal hyperplasia in vivo. Silencing of miR-146a in VSMCs increases KLF4 expression, whereas overexpression of miR-146a decreases KLF4 levels. Furthermore, we demonstrate that KLF4 competes with Krüppel-like factor 5 (KLF5) to bind to and regulate the miR-146a promoter, and that KLF4 and KLF5 exert opposing effects on the miR-146a promoter. Overexpression of KLF4 in VSMCs decreases miR-146a transcription levels. By using both gain-of-function and loss-of-function approaches, we found that miR-146a promotes VSMC proliferation in vitro. Transfection of antisense miR-146a oligonucleotide into balloon-injured rat carotid arteries markedly decreased neointimal hyperplasia. These findings suggest that miR-146a and KLF4 form a feedback loop to regulate each other's expression and VSMC proliferation.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
1469-3178
|
pubmed:author | |
pubmed:issnType |
Electronic
|
pubmed:volume |
12
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
56-62
|
pubmed:dateRevised |
2011-3-16
|
pubmed:meshHeading |
pubmed-meshheading:21109779-Animals,
pubmed-meshheading:21109779-Base Sequence,
pubmed-meshheading:21109779-Cell Proliferation,
pubmed-meshheading:21109779-Feedback, Physiological,
pubmed-meshheading:21109779-Humans,
pubmed-meshheading:21109779-Hyperplasia,
pubmed-meshheading:21109779-Kruppel-Like Transcription Factors,
pubmed-meshheading:21109779-Male,
pubmed-meshheading:21109779-MicroRNAs,
pubmed-meshheading:21109779-Molecular Sequence Data,
pubmed-meshheading:21109779-Myocytes, Smooth Muscle,
pubmed-meshheading:21109779-Neointima,
pubmed-meshheading:21109779-RNA Interference,
pubmed-meshheading:21109779-Rats,
pubmed-meshheading:21109779-Rats, Sprague-Dawley,
pubmed-meshheading:21109779-Sequence Alignment,
pubmed-meshheading:21109779-Transcription, Genetic
|
pubmed:year |
2011
|
pubmed:articleTitle |
miR-146a and Krüppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation.
|
pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang 050017, China.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|