Upregulation of OGT-mediated EZH2 O-GlcNAcylation Promotes Human Umbilical Vein Endothelial Cell Proliferation, Invasion, Migration, and Tube Formation in Gestational Diabetes Mellitus.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2025-01-03 DOI:10.1007/s12013-024-01655-5

Yu Qiu, Weiwei Yu, Xueqin Zhang, Mingjing Zhang, Yan Ni, Shaoyang Lai, Quanfeng Wu

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引用次数: 0

Abstract

O-linked N-acetylglucosamine transferase (OGT)-catalyzed O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) is closely associated with diabetes progression. This study aims to investigate the mechanism of OGT in regulating endothelial dysfunction in gestational diabetes mellitus (GDM). Expressions of OGT, O-linked N-acetylglucosamine (O-GlcNAc), enhancer of zeste homolog 2 (EZH2), and HEK27me3 in human umbilical vein endothelial cells (HUVECs) and GDM-derived HUVECs (GDM-HUVECs) were assessed by western blot. RT-qPCR and western blot assays were used to test the OGT overexpression and EZH2 silencing levels. CCK-8, EdU, wound healing, and transwell invasion assays were used to analyze the cell proliferative, migratory, and invasive abilities. Tube formation assay was performed to evaluate angiogenesis ability of cells. Western blot assay was performed to estimate vascular endothelial growth factor (VEGF) and p-VEGFR2 levels in cells. The binding of O-GlcNAc and EZH2 after OGT overexpression was measured by Co-IP assay. The results showed that OGT, O-GlcNAc, EZH2, and HEK27me3 expressions were declined in GDM-HUVECs. OGT overexpression induced the proliferation, migration, and invasion of GDM-HUVECs, and also elevated angiogenesis and the expressions of VEGF and p-VEGFR2 in cells. O-GlcNAc, EZH2, and HEK27me3 expressions were upregulated after OGT overexpression. OGT upregulation induced the binding between O-GlcNAc and EZH2. EZH2 silencing attenuated the promotion of OGT overexpression on the proliferative, invasive, migratory, and angiogenic capacities of GDM-HUVECs. To be concluded, OGT overexpression stabilized EZH2 expression by promoting O-GlcNAcylation modification of EZH2, and further enhanced proliferation, migration, and invasion as well as angiogenesis of GDM-HUVECs. While these effects were decayed after EZH2 absenting. Overall, the modulation of OGT on endothelial dysfunction in GDM provides a novel perspective for the clinical treatment of GDM.

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来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.