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C-terminal binding protein 2 promotes high-glucose-triggered cell proliferation, angiogenesis and cellular adhesion of human retinal endothelial cell line

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Abstract

Purpose

The proliferation and angiogenesis of human retinal endothelial cells (HRECs) are critical for the pathophysiology of diabetic retinopathy (DR). C-terminal binding protein 2 (CtBP2) has multiple biologic functions, but its effect on HRECs under high-glucose (HG) conditions is unclear.

Methods

The cell viability, angiogenesis, cellular adhesion and CtBP2 expression levels of HRECs were measured following treatment with different concentrations of glucose. Small interfering CtBP2-targeting RNA, wide-type and function mutant plasmid of CtBP2 were constructed and then were transfected into HRECs to evaluate the effects of CtBP2 on cell functions of HRECs.

Results

The expression of CtBP2 in HRECs was increased after HG treatment. HG treatment significantly increased cell proliferation, angiogenesis, and decreased relative gene expressions in gap junctions, tight junctions and adherens junctions. After CtBP2 was inhibited via siRNA, the changes induced by HG were partially restored. Conversely, only wild-type CtBP2 could increase cell proliferation and angiogenesis under HG condition. Mechanistically, we also found that CtBP2 exerted its functions to effect HG-induced changes via Akt signaling pathway.

Conclusion

This study implicates that CtBP2 promotes HG-induced cell proliferation, angiogenesis and cellular adhesion, and CtBP2 might be a potential target in the prevention of DR.

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Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Abbreviations

DR:

Diabetic retinopathy

HRECs:

Human retinal endothelial cells

CtBP2:

C-terminal binding protein 2

GJs:

Gap junctions

TJs:

Tight junctions

AJs:

Adherens junctions

HG:

High glucose

LG:

Low glucose

MAPK:

Mitogen-activated protein kinase

PI3K:

Phosphatidylinositol-3-kinase

VEGF:

Vascular endothelial growth factor

qRT-PCR:

Real-time quantitative reverse transcription PCR

ZEB1:

Zinc finger E-box binding homeobox 1

TNF-α:

Tumor necrosis factor alpha

ZO-1:

Zonula occludens-1

NADH:

Nicotinamide adenine dinucleotide

PTEN:

Phosphatase and tensin homolog

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Acknowledgements

The abstract of this manuscript has been presented in Abstracts from “The 24th Congress of Chinese Ophthalmological Society Suzhou, China September 4-8, 2019”.

Funding

This study was funded by the National Natural Science Foundation of China (81500706), the Postdoctoral Science Foundation of China (2020M671562), the Postdoctoral Science Foundation of Jiangsu Province (2020Z318), the Science and Technology Project of Nantong Municipality (YYZ17010 and HS2020005).

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Author notes

  1. Han Li, Feng Zhou have contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

    Han Li, Feng Zhou, Xingjian Cao, Ping Zhao, Wei Xie & Xiang Chen

  2. Department of Ophthalmology, The Second Affiliated Hospital of Nantong University, Nantong, China

    Xiaobo Huang

  3. Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

    Guowei Zhang

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  1. Han Li
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Contributions

XC designed this research. HL, FZ and XC performed experiments and drafted this manuscript. PZ and XH collected tissues samples and analyzed clinical data. WX assisted with part of cell and animal experiments. GZ edited the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Guowei Zhang or Xiang Chen.

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Li, H., Zhou, F., Cao, X. et al. C-terminal binding protein 2 promotes high-glucose-triggered cell proliferation, angiogenesis and cellular adhesion of human retinal endothelial cell line. Int Ophthalmol 42, 2975–2985 (2022). https://doi.org/10.1007/s10792-022-02283-9

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