Abstract |
Lipopolysaccharide (LPS) can induce vascular endothelial injury. Circular RNAs ( circRNAs) have been verified to regulate different cellular processes in various diseases. This study intended to explore the potential role and mechanism of circ_0057583 in brain microvascular endothelial cell injury. Human brain microvascular endothelial cells (hBMECs) were exposed to different doses of LPS to induce cell damage. The levels of circ_0057583, microRNA-204-5p (miR-204-5p) and nuclear receptor 4A1 (NR4A1) were detected by quantitative real-time PCR or Western blot assays. Cell viability, apoptosis, inflammation and angiogenesis were assessed by Counting Kit-8 (CCK-8), flow cytometry, enzyme linked immunosorbent assay (ELISA) and tube formation assays. The targeting relationship between miR-204-5p and circ_0057583 or NR4A1 was verified by dual- luciferase reporter assay and RNA immunoprecipitation (RIP) assay. LPS treatment elevated the expression of circ_0057583 and NR4A1, but decreased the expression of miR-204-5p in LPS-induced hBMECs. Downregulation of circ_0057583 abated LPS-induced hBMEC injury by inducing cell proliferation and angiogenesis, as well as inhibiting cell apoptosis, autophagy and inflammation. Circ_0057583 aggravated LPS-evoked hBMEC injury by regulating miR-204-5p. Also, miR-204-5p suppressed LPS-evoked hBMEC damage via targeting NR4A1. Moreover, circ_0057583 sponged miR-204-5p to up-regulate NR4A1 level. Depletion of circ_0057583 alleviated LPS-triggered brain microvascular endothelial endothelial cell injury through modulating miR-204-5p/NR4A1 axis.
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Authors | Xiaoyu Wang, Lili Liu, Lei Zhang, Jing Guo, Lixia Yu, Tao Li |
Journal | Metabolic brain disease
(Metab Brain Dis)
Vol. 37
Issue 2
Pg. 501-511
(02 2022)
ISSN: 1573-7365 [Electronic] United States |
PMID | 34767155
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. |
Chemical References |
- MIRN204 microRNA, human
- MicroRNAs
- NR4A1 protein, human
- Nuclear Receptor Subfamily 4, Group A, Member 1
- RNA, Circular
- Receptors, Cytoplasmic and Nuclear
- HECW2 protein, human
- Ubiquitin-Protein Ligases
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Topics |
- Brain
(metabolism)
- Endothelial Cells
(metabolism, pathology)
- Humans
- MicroRNAs
(metabolism)
- Nuclear Receptor Subfamily 4, Group A, Member 1
(metabolism)
- RNA, Circular
(genetics)
- Receptors, Cytoplasmic and Nuclear
(metabolism)
- Ubiquitin-Protein Ligases
(genetics)
|