Transcription factor FOXP1 mediates vascular endothelial dysfunction in diabetic retinopathy

Zhou, Yekai; Xuan, Yaling; Liu, Yi; Zheng, Junfang; Jiang, Xiaoyun; Zhang, Yun; Jian, Zhao; Li, Yanli; An, Meixia

doi:10.1007/s00417-022-05698-3

Cited by 4 publications

(1 citation statement)

References 29 publications

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“…DR is emerging as the number one blinding eye disease in the working population [1,2]. The main features of this disease are that under the stimulation of persistent hyperglycemia, the retinal vascular permeability of diabetic patients increases, retinal microvascular endothelial cells become dysfunctional, their proliferative capacity is enhanced, and the secretion of angiogenic mediators increases, leading to the massive generation of microvessels [3]. Studies have shown that DR progression is associated with abnormal migration, proliferation, and microvessel formation in human retinal microvascular endothelial cells (HRMECs) [4].…”

Section: Introductionmentioning

confidence: 99%

NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation

Wang,

Xue,

Kan

et al. 2024

J Transl Med

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Background Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m5C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m5C methylation, on the progression of DR. Method Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. Results The levels of both NSUN2 and RNA m5C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m5C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. Conclusions NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m5C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.

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Section: Introductionmentioning

confidence: 99%

NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation

Wang,

Xue,

Kan

et al. 2024

J Transl Med

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The functions of FOXP transcription factors and their regulation by post-translational modifications

Gao,

Zhu,

Gong

et al. 2023

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Bone marrow mesenchymal stem cell‐derived exosomal miR‐221‐3p promotes angiogenesis and wound healing in diabetes via the downregulation of forkhead box P1

Qiu,

Xu,

Liang

2024

Diabet Med

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AimImpaired wound healing in patients with diabetes can develop into nonhealing ulcerations. Because bone marrow mesenchymal stem cells (BMSCs) exosomes can promote wound healing, this study aims to investigate the mechanism of BMSCs‐isolated exosomal miR‐221‐3p in angiogenesis and diabetic wound healing.MethodsTo mimic diabetes in vitro, human umbilical vein endothelial cells (HUVECs) were subjected to high glucose (HG). Exosomes were derived from BMSCs and identified by transmission electron microscopy (TEM), western blot analysis and dynamic light scattering (DLS). The ability to differentiate BMSCs was assessed via Oil red O staining, alkaline phosphatase (ALP) staining and alizarin red staining. The ability to internalise PKH26‐labelled exosomes was assessed using confocal microscopy. Migration, cell viability and angiogenesis were tested by scratch, MTT and tube formation assays separately. The miRNA and protein levels were analysed by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) or western blotting. The relationship among miR‐221‐3p, FOXP1 and SPRY1 was determined using the dual‐luciferase reporter, ChIP and RIP assays.ResultsExosomal miR‐221‐3p was successfully isolated from BMSCs and delivered into HUVECs. HG was found to suppress the angiogenesis, cell viability and migration of HUVECs and exosomal miR‐221‐3p separated from BMSCs inhibited the above phenomenon. FOXP1 could transcriptionally upregulate SPRY1, and the silencing of FOXP1 reversed the HG‐stimulated angiogenesis inhibition, cell viability and migration in HUVECs via the downregulation of SPRY1. Meanwhile, miR‐221‐3p directly targeted FOXP1 and the overexpression of FOXP1 reversed the positive effect of exosomal miR‐221‐3p on HUVEC angiogenesis.ConclusionExosomal miR‐221‐3p isolated from BMSCs promoted angiogenesis in diabetic wounds through the mediation of the FOXP1/SPRY1 axis. Furthermore, the findings of this study can provide new insights into probing strategies against diabetes.

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Transcription factor FOXP1 mediates vascular endothelial dysfunction in diabetic retinopathy

Cited by 4 publications

References 29 publications

NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation

NSUN2 affects diabetic retinopathy progression by regulating MUC1 expression through RNA m5C methylation

The functions of FOXP transcription factors and their regulation by post-translational modifications

Bone marrow mesenchymal stem cell‐derived exosomal miR‐221‐3p promotes angiogenesis and wound healing in diabetes via the downregulation of forkhead box P1

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