Upregulation of OGT-mediated EZH2 O-GlcNAcylation Promotes Human Umbilical Vein Endothelial Cell Proliferation, Invasion, Migration, and Tube Formation in Gestational Diabetes Mellitus
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View abstract on PubMed
Summary
This summary is machine-generated.O-linked N-acetylglucosamine transferase (OGT) enhances endothelial cell function in gestational diabetes mellitus (GDM) by stabilizing EZH2 through O-GlcNAcylation. This improves proliferation, migration, and angiogenesis, offering a new therapeutic target for GDM.
Area Of Science
- Endocrinology and Metabolism
- Cell Biology
- Vascular Biology
Background
- O-linked N-acetylglucosamine transferase (OGT)-catalyzed O-GlcNAcylation is linked to diabetes progression.
- Endothelial dysfunction is a hallmark of gestational diabetes mellitus (GDM).
- The precise role of OGT in GDM-induced endothelial dysfunction requires elucidation.
Purpose Of The Study
- To investigate the mechanism by which OGT regulates endothelial dysfunction in GDM.
- To explore the interaction between OGT, O-GlcNAcylation, and EZH2 in GDM endothelial cells.
Main Methods
- Assessed protein expression (OGT, O-GlcNAc, EZH2, H3K27me3) in HUVECs and GDM-HUVECs via Western blot.
- Utilized RT-qPCR for gene expression analysis.
- Evaluated cell proliferation, migration, invasion, and angiogenesis using CCK-8, EdU, wound healing, Transwell, and tube formation assays.
- Investigated protein interactions using Co-immunoprecipitation (Co-IP).
Main Results
- GDM-HUVECs exhibited reduced expression of OGT, O-GlcNAc, EZH2, and H3K27me3.
- OGT overexpression in GDM-HUVECs promoted proliferation, migration, invasion, and angiogenesis, increasing VEGF and p-VEGFR2 levels.
- OGT overexpression upregulated O-GlcNAc and EZH2, enhancing O-GlcNAc binding to EZH2.
- Silencing EZH2 diminished the pro-proliferative, pro-migratory, pro-invasive, and pro-angiogenic effects of OGT overexpression.
Conclusions
- OGT overexpression stabilizes EZH2 via O-GlcNAcylation, thereby enhancing proliferation, migration, invasion, and angiogenesis in GDM endothelial cells.
- EZH2 is crucial for mediating the beneficial effects of OGT in GDM endothelial dysfunction.
- Targeting OGT offers a potential therapeutic strategy for managing endothelial dysfunction in GDM.
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