Role of miR-21-5p/FilGAP axis in estradiol alleviating the progression of monocrotaline-induced pulmonary hypertension.
Animal Model Exp Med
; 5(3): 217-226, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35713208
ABSTRACT
BACKGROUND:
Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH.METHODS:
Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 µg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline-induced PH (MCT-PH) male rats were treated with 17ß-estradiol (E2 ) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA.RESULTS:
Many circulating miRNAs, including miR-21-5p and miR-574-5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR-21-5p in the lungs was significantly upregulated in MCT-PH rats compared with the controls. However, miR-574-5p showed no difference in the lungs of MCT-PH rats and controls. miR-21-5p was selected for further analysis in rats as E2 strongly regulated it. E2 decreased miR-21-5p expression in the lungs of MCT-PH rats by ERß. E2 reversed miR-21-5p target gene FilGAP downregulation in the lungs of MCT-PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c-Jun in the lungs of MCT-PH rats was inhibited by E2 and miR-21-5p antagonist.CONCLUSIONS:
miR-21-5p level was remarkably associated with PH severity in patients. Moreover, the miR-21-5p/FilGAP signaling pathway modulated the protective effect of E2 on MCT-PH through ERß.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Activadoras de GTPasa
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MicroARNs
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Estradiol
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Hipertensión Pulmonar
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Animal Model Exp Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
China