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Graefe's Archive for Clinical and Experimental Ophthalmology

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13-06-2022 | Diabetic Retinopathy | Basic Science

Transcription factor FOXP1 mediates vascular endothelial dysfunction in diabetic retinopathy

Authors: Yekai Zhou, Yaling Xuan, Yi Liu, Jiaxuan Zheng, Xiaoyun Jiang, Yun Zhang, Jian Zhao, Yanli Liu, Meixia An

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 12/2022

Abstract

Background

Diabetic retinopathy (DR) is still the fastest growing cause of blindness in working aged adults, and its typical characteristics are endothelial cell dysfunction and pericytes loss. Transcription factor fork head box P1 (FOXP1) is a member of FOX family involved in diabetes progression and is expressed in endothelial cells. The purpose of this study was to investigate the role and mechanism of FOXP1 in DR.

Methods

The vitreous of DR patients and non-DR patients were collected, and the expression of FOXP1 was detected by real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) cultured in high glucose simulated DR environment, and the expressions of FOXP1, vascular endothelial growth factor (VEGF), and pigment epithelium derived factor (PEDF) were detected by RT-qPCR and western blot (WB) after transfection of small interfering RNA (siRNA) to knock out FOXP1. At the same time, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT), 5-ethynyl-2′-deoxyuridine assay (EDU), flow cytometry, Transwell assay, and tube-forming experiment were performed to determine cell proliferation, migration, and tube-forming ability.

Results

We found that FOXP1 was highly expressed in the vitreous of DR patients and HUVECs under high glucose condition. After FOXP1 was decreased, the activation of VEGF expression and inhibition of PEDF expression in HUVECs induced by high glucose were reversed; meanwhile, cell proliferation, migration, and tube formation decreased, and apoptosis was promoted.

Conclusion

Generally, FOXP1 is highly expressed in the vitreous of DR patients, and its silence prevented VEGF/PEDF signaling pathway stimulated by high glucose and also reduced the proliferation, migration, and tube formation of endothelial cell, thus improving vascular endothelial dysfunction caused by DR. The results indicate that FOXP1 may be a therapeutic target of DR.

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Title: Transcription factor FOXP1 mediates vascular endothelial dysfunction in diabetic retinopathy
Authors: Yekai Zhou
Yaling Xuan
Yi Liu
Jiaxuan Zheng
Xiaoyun Jiang
Yun Zhang
Jian Zhao
Yanli Liu
Meixia An
Publication date: 13-06-2022
Publisher: Springer Berlin Heidelberg
Keywords: Diabetic Retinopathy
Diabetic Retinopathy
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 12/2022
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-022-05698-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Transcription factor FOXP1 mediates vascular endothelial dysfunction in diabetic retinopathy

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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