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.

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.

• Authors: Qianqian Wan, Heting Liu, Yuxin Xu, Qing Zhang, Liming Tao
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 22 Issue 3 Pg. 331-346 (02 2023) ISSN: 1551-4005 [Electronic] United States
• PMID: 36200131 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vascular Endothelial Growth Factor A
• MicroRNAs
• Vascular Endothelial Growth Factors
• Tight Junction Proteins
• SOX17 protein, human
• SOXF Transcription Factors
• MIRN194 microRNA, human
• Sox17 protein, mouse
• HMGB Proteins

Topics

• Humans
• Mice
• Animals
• Vascular Endothelial Growth Factor A (metabolism)
• MicroRNAs (genetics, metabolism)
• Endothelial Cells (metabolism)
• Cell Proliferation
• Vascular Endothelial Growth Factors (metabolism, pharmacology)
• Hypertensive Retinopathy (metabolism, pathology)
• Tight Junction Proteins (metabolism)
• SOXF Transcription Factors (genetics, metabolism, pharmacology)
• HMGB Proteins (metabolism, pharmacology)