Long noncoding RNA MALAT1 contributes to pregnancy-induced hypertension development by enhancing oxidative stress and inflammation through the regulation of the miR-150-5p/ET-1 axis.
FASEB J
; 34(5): 6070-6085, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32246794
ABSTRACT
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified previously in the pathogenesis of hypertension and some gestational diseases. However, the biological functions of MALAT1 in pregnancy-induced hypertension (PIH) are still poorly understood. Herein, we aim to explore the functional relevance of MALAT1 in PIH and to explain the potential underlying mechanisms. We found that the levels of ET-1 and MALAT1 were upregulated and that of miR-150-5p were downregulated in the serum of pregnant women with PIH and the aortic endothelial cells (ECs) of reduced uterine perfusion pressure (RUPP)-induced rat models. In aortic ECs, MALAT1 could competitively bind to miR-150-5p to upregulate the expression of ET-1. The MALAT1/miR-150-5p/ET-1 axis regulated the expression of endothelin B receptor (ETBR) in aortic ECs leading to oxidative stress imbalance and increased the release of proinflammatory cytokines (IL-18 and IL-1ß), which concurrently activated the NF-κB pathway to regulate the ETBR expression and to stimulate smooth muscle cell (SMC) contraction. Furthermore, silencing MALAT1 could alleviate the hypertensive symptoms of RUPP-induced rat models. Taken conjointly, the upregulation of MALAT1 can reduce the expression of ET-1 by competitively binding to miR-150-5p, which enhances the expression of ETBR via the activation of the NF-κB pathway in SMCs, thus exacerbating the hypertensive symptoms in the RUPP-induced rat models.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Estresse Oxidativo
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Endotelina-1
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MicroRNAs
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Hipertensão Induzida pela Gravidez
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RNA Longo não Codificante
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Inflamação
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article