MicroRNA 573 Rescues Endothelial Dysfunction during Dengue Virus Infection under PPARγ Regulation.
J Virol
; 96(6): e0199621, 2022 03 23.
Article
em En
| MEDLINE
| ID: mdl-35108097
ABSTRACT
Early prognosis of abnormal vasculopathy is essential for effective clinical management of patients with severe dengue. An exaggerated interferon (IFN) response and release of vasoactive factors from endothelial cells cause vasculopathy. This study shows that dengue virus 2 (DENV2) infection of human umbilical vein endothelial cells (HUVEC) results in differentially regulated microRNAs (miRNAs) important for endothelial function. miR-573 was significantly downregulated in DENV2-infected HUVEC due to decreased peroxisome proliferator activator receptor gamma (PPARγ) activity. Restoring miR-573 expression decreased endothelial permeability by suppressing the expression of vasoactive angiopoietin 2 (ANGPT2). We also found that miR-573 suppressed the proinflammatory IFN response through direct downregulation of Toll-like receptor 2 (TLR2) expression. Our study provides a novel insight into miR-573-mediated regulation of endothelial function during DENV2 infection, which can be further translated into a potential therapeutic and prognostic agent for severe dengue patients. IMPORTANCE We need to identify molecular factors that can predict the onset of endothelial dysfunction in dengue patients. Increase in endothelial permeability during severe dengue infections is poorly understood. In this study, we focus on factors that regulate endothelial function and are dysregulated during DENV2 infection. We show that miR-573 rescues endothelial permeability and is downregulated during DENV2 infection in endothelial cells. This finding can have both diagnostic and therapeutic applications.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
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Dengue Grave
/
Vírus da Dengue
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MicroRNAs
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PPAR gama
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article