LncRNA NKILA regulates endothelium inflammation by controlling a NF-κB/KLF4 positive feedback loop.
J Mol Cell Cardiol
; 126: 60-69, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30419187
ABSTRACT
Endothelium inflammation, a key event in vascular pathological process, can lead to endothelial activation and subsequent vascular disorders. Long non-coding RNA NKILA plays an important regulatory role in pro-inflammatory response. However, the underlying molecular basis by which NKILA regulates endothelial inflammation is poorly understood. In this study, we identify NKILA as a critical repressor to protect the endothelium from inflammation. Mechanistically, we show that NKILA is able to positively mediate the expression of KLF4, an anti-inflammatory atheroprotective regulator in endothelial cells (ECs), by a NF-κB-mediated DNA methylation mechanism. Moreover, NF-κB is found to help recruit DNMT3A to the CpG island of KLF4 promoter, facilitating KLF4 promoter DNA methylation and transcriptional repression. More importantly, we find KLF4 can inversely attenuate NF-κB transcriptional activity via establishing a NF-κB/KLF4 positive feedback loop, which is under the control of NKILA. Hence, sustained endothelium inflammation will occur, once the NKILA becomes dysfunctional. These studies revealed that NKILA can function as a vital regulator to protect the endothelium from inflammatory lesions and related vascular diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
NF-kappa B
/
Retroalimentação Fisiológica
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Fatores de Transcrição Kruppel-Like
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RNA Longo não Codificante
/
Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article