FGF21 attenuates hypoxiainduced dysfunction and inflammation in HPAECs via the microRNA27bmediated PPARγ pathway.
Int J Mol Med
; 47(6)2021 06.
Article
em En
| MEDLINE
| ID: mdl-33907846
ABSTRACT
Pulmonary arterial hypertension (PAH), is a chronic and progressive disorder characterized by pulmonary vascular remodeling, including endothelial cell dysfunction and inflammation. MicroRNAs (miRNAs or miRs) play an important role in the development of PAH. In addition, fibroblast growth factor 21 (FGF21) has been found to have marked anti-dysfunction and antiinflammatory properties. Therefore, the present study aimed to investigate the latent effects of FGF21 against PAH through the miR27b/peroxisome proliferatoractivated receptor γ (PPARγ) axis. Human pulmonary arterial endothelial cells (HPAECs) subjected to hypoxia were used as PAH models. The results revealed that PPARγ expression was downregulated and miR27b expression was upregulated in the HPAECs exposed to hypoxia. Luciferase assay suggested that PPARγ was a target gene of miR27b. Furthermore, miR27b inhibited the expression of the PPARγ gene, thereby aggravating hypoxiainduced HPAEC dysfunction. Moreover, miR27b activated the nuclear factorκB signaling pathway and the expression of inflammatory factors [interleukin (IL)1ß, IL6 and tumor necrosis factorα] by targeting PPARγ. In addition, the expression of miR27b decreased following treatment of the hypoxiaexposed HPAECs with FGF21. Furthermore, FGF21 alleviated hypoxiainduced HPAEC dysfunction and inflammation by inhibiting miR27b expression and thereby promoting PPARγ expression. On the whole, the findings of the present study suggest that FGF21 may serve as a therapeutic target for managing PAH through the miR27bmediated PPARγ pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
/
Transdução de Sinais
/
MicroRNAs
/
Células Endoteliais
/
PPAR gama
/
Fatores de Crescimento de Fibroblastos
/
Inflamação
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article