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MicroRNA-217 ameliorates inflammatory damage of endothelial cells induced by oxidized LDL by targeting EGR1

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Abstract

Oxidized low-density lipoprotein (ox-LDL) modulates gene transcription and expression and induces the development of endothelium inflammation and endothelial dysfunction, in which microRNAs (miRNAs) play a crucial role. However, the mechanism of ox-LDL in inflammatory damage of endothelial cells still remains elusive. Herein, we focused on the effect of hsa-miR-217-5p (miR-217) on endothelial dysfunction induced by ox-LDL by targeting early growth response protein-1 (EGR1). In the present study, 31 upregulated miRNAs and 59 downregulated miRNAs (Fold Change > 2, P value < 0.05) were identified after 6 h of 80 μg/mL ox-LDL exposure in human aortic endothelial cells (HAECs) by small RNA sequencing, including miR-217 that was significantly decreased (FC = 0.2787, P value = 5.22E-16). MiR-217 knockdown inhibited cell proliferation and increased level of IL-6, IL-1β, ICAM-1 and TNF-α, while overexpression of miR-217 relieved the growth inhibition induced by ox-LDL and demonstrated anti-inflammatory effect in HAECs. EGR1 was predicted as a potential candidate target gene of miR-217 by TargetScan. The subsequent dual-luciferase reporter assay confirmed the direct binding of miR-217 to 3′UTR of EGR1. And EGR1 expression was negatively correlated with the level of miRNA-217 in HAECs after exposure to ox-LDL. Overexpression of EGR1 recapitulated the effects of miR-217 knockdown on cell proliferation inhibition and inflammation in HAECs, while knockdown EGR1 relieved the proliferative inhibition and demonstrated anti-inflammatory effect in ox-LDL-induced HAECs. The present study confirmed miR-217 ameliorates inflammatory damage of endothelial cells induced by oxidized LDL by targeting EGR1.

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modified by exogenous change in miR-217 in HAECs. *P < 0.05, **P < 0.01 vs miRNA-NC. d Relative mRNA expression (qRT-PCR) of IL-6, IL-1β, ICAM-1 and TNF-α was increased after ox-LDL exposure. **P < 0.01 vs untreated HAECs. e Relative mRNA expression (qRT-PCR) of IL-6, IL-1β, ICAM-1 and TNF-α after exogenous change in miR-217 in HAECs was determined by qRT-PCR. *P < 0.05, **P < 0.01 vs miRNA-NC. f Levels of IL-6, IL-1β, ICAM-1 and TNF-α in supernatant (ELISA) were increased after ox-LDL exposure. *P < 0.05, **P < 0.01 vs untreated HAECs. g Levels of IL-6, IL-1β, ICAM-1 and TNF-α in supernatant after exogenous change in miR-217 were determined by ELISA. *P < 0.05, **P < 0.01 vs miRNA-NC. n = 3

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Acknowledgements

We thank Ms Qian Zhou of Shanghai Genomeditech Corporation for technical assistance.

Funding

This study was supported by the National Natural Science Foundation of China No. 81673807 and ‘Taishan Scholar’ Project of Shandong Province No. 2018-35.

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Authors and Affiliations

  1. Vascular Surgery Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369, Jingshi Road, Jinan, 250011, China

    Xuesong Yang

  2. Cardiovascular Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369, Jingshi Road, Jinan, 250011, China

    Dongna Li, Wenjing Chen & Chuan-Hua Yang

  3. Health College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China

    Ying-Zi Qi

  4. Central Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369, Jingshi Road, Jinan, 250011, China

    Yue-Hua Jiang

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Contributions

YXS performed the experiments and drafted the manuscript. LDN contributed small RNA sequencing and transfection. QYZ participated in the data interpretation and discussion. CWJ contributed to software applications and data analysis. YCH and JYH designed the study and carried out important revisions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Chuan-Hua Yang or Yue-Hua Jiang.

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Yang, X., Li, D., Qi, YZ. et al. MicroRNA-217 ameliorates inflammatory damage of endothelial cells induced by oxidized LDL by targeting EGR1. Mol Cell Biochem 475, 41–51 (2020). https://doi.org/10.1007/s11010-020-03857-w

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