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Combinatorial Chemistry & High Throughput Screening

Author(s): Jian Li, Mingzhu Wang, Xiaoling Wu, Nanzi Xie, Haifeng Wang, Junling Huang, Fei Sheng* and Wenlin Ma*

DOI: 10.2174/1386207326666230509100019

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miR-129-5p/FGF2 Axis is Associated with Homocysteine-induced Human Umbilical Vein Endothelial Cell Injury

Page: [641 - 648] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Purpose: Homocysteine (Hcy)-induced endothelial cell injury is a key event in atherosclerosis pathogenesis. In this study, we aimed to explore the mechanisms underlying Hcy-induced endothelial injury by assessing the effects of Hcy on endothelial cell proliferation and the microRNA (miR)-129-5p/fibroblast growth factor 2 (FGF2) axis.

Methods: Human umbilical vein endothelial cells (HUVECs) were treated with Hcy to construct an endothelial cell injury model. Expression levels of FGF2 in Hcy-induced HUVECs were determined using quantitative real-time polymerase chain reaction and western blotting. An FGF2 overexpression lentiviral vector was constructed to upregulate FGF2 expression in HUVECs via lentivirus transduction. A cell counting kit-8 assay was used to explore the effects of FGF2 overexpression on HUVEC proliferation. An upstream regulatory miRNA was predicted, and its targetbinding relationship with FGF2 was evaluated using a dual-luciferase reporter assay.

Results: We found that FGF2 expression in HUVECs was inhibited by Hcy treatment. Lentivirus transduction led to the overexpression of FGF2 in HUVECs, which significantly reversed the effect of Hcy on endothelial cell proliferation. miR-129-5p was experimentally validated as an upstream regulator of FGF2, and its decreased levels in HUVECs led to increased FGF2 expression. In addition, HUVEC proliferation was enhanced by the knockdown of miR-129-5p, and this effect was reversed by Hcy treatment.

Conclusion: Taken together, the results of this study revealed that Hcy inhibits FGF2 expression in HUVECs, and FGF2 is regulated by upstream miR-129-5p to improve the effect of Hcy on endothelial cell proliferation.

Graphical Abstract

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