miR-146a and Krüppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation.
EMBO Rep
; 12(1): 56-62, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-21109779
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Retroalimentação Fisiológica
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Miócitos de Músculo Liso
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MicroRNAs
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Proliferação de Células
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Fatores de Transcrição Kruppel-Like
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article