Upregulated miR-194-5p suppresses retinal microvascular endothelial cell dysfunction and mitigates the symptoms of hypertensive retinopathy in mice by targeting SOX17 and VEGF signaling.
Cell Cycle
; 22(3): 331-346, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36200131
ABSTRACT
BACKGROUND:
Hypertensive retinopathy (HR) is a retinal disease that may lead to vision loss and blindness. Sex-determining region Y (SRY)-box (SOX) family transcription factors have been reported to be involved in HR development. In this study, the role and upstream mechanism of SRY-box transcription factor 17 (SOX17) in HR pathogenesis were investigated.METHODS:
SOX17 and miR-194-5p levels in Angiotensin II (Ang II)-stimulated human retinal microvascular endothelial cells (HRMECs) and retinas of mice were detected by RT-qPCR. SOX17 protein level as well as levels of tight junction proteins and vascular endothelial growth factor (VEGF) signaling-associated proteins were quantified by western blotting. Tube formation assays were performed to evaluate angiogenesis in HRMECs. The structure of mouse retinal tissues was observed by H&E staining. The interaction between miR-194-5p and SOX17 was confirmed by a luciferase reporter assay.RESULTS:
SOX17 was upregulated in HRMECs treated with Ang II. SOX17 knockdown inhibited angiogenesis in Ang II-stimulated HRMECs and increased tight junction protein levels. Mechanically, SOX17 was targeted by miR-194-5p. Moreover, miR-194-5p upregulation restrained angiogenesis and increased tight junction protein levels in Ang II-treated HRMECs, and the effect was reversed by SOX17 overexpression. MiR-194-5p elevation inactivated VEGF signaling via targeting SOX17. miR-194-5p alleviated pathological symptoms of HR in Ang II-treated mice, and its expression was negatively correlated with SOX17 expression in the retinas of model mice.CONCLUSIONS:
MiR-194-5p upregulation suppressed Ang II-stimulated HRMEC dysfunction and mitigates the symptoms of HR in mice by regulating the SOX17/VEGF signaling.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Retinopatia Hipertensiva
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China