Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis

Autor: Zixuan Wang, Xicheng Wang, Meihua Hao, Taisheng Wu, Shuang-Zhan Li, Lei Zhang, Junjian Zhang
Rok vydání: 2020
Předmět:
0301 basic medicine
Anti-Inflammatory Agents
Inflammation
Apoptosis
RM1-950
medicine.disease_cause
Antioxidants
Ox-LDL
Superoxide dismutase
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
CircNOL12
MiR-6873-3p
Downregulation and upregulation
medicine
Human Umbilical Vein Endothelial Cells
Humans
Kaempferols
HUVECs
Adaptor Proteins
Signal Transducing
Pharmacology
chemistry.chemical_classification
Reactive oxygen species
Kae
biology
FRS2
Endothelial Cells
Membrane Proteins
Nuclear Proteins
RNA-Binding Proteins
General Medicine
Malondialdehyde
Molecular biology
Endothelial stem cell
MicroRNAs
Oxidative Stress
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
biology.protein
Female
Therapeutics. Pharmacology
medicine.symptom
Reactive Oxygen Species
Oxidative stress
Signal Transduction
Zdroj: Biomedicine & Pharmacotherapy, Vol 137, Iss, Pp 111419-(2021)
ISSN: 1950-6007
Popis: Background Atherosclerosis, inflammatory disease, is a major reason for cardiovascular diseases and stroke. Kaempferol (Kae) has been well-documented to have pharmacological activities in the previous studies. However, the detailed mechanisms by which Kae regulates inflammation, oxidative stress, and apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) remain unknown. Methods and results The real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure expression levels of circNOL12, nucleolar protein 12 (NOL12), miR-6873-3p, and Fibroblast growth factor receptor substrate 2 (FRS2) in HUVECs treated with either oxidized low-density lipoprotein (ox-LDL) alone or in combination with Kae. The cells viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)−2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay. The inflammation and oxidative stress were assessed by checking inflammatory factors, Reactive Oxygen Species (ROS), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) levels in ox-LDL-induced HUVECs. The apoptotic cells were quantified by flow cytometry assay. The western blot assay was used for measuring protein expression. The interaction relationship between miR-6873-3p and circNOL12 or FRS2 was analyzed by dual-luciferase reporter and RNA pull-down assays. Treatment with Kae could inhibit ox-LDL-induced the upregulation of circNOL12 in HUVECs. Importantly, Kae weakened ox-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs, which was abolished by overexpression of circNOL12. What’s more, miR-6873-3p was a target of circNOL12 in HUVECs, and the upregulation of miR-6873-3p overturned circNOL12 overexpression-induced effects on HUVECs treated with ox-LDL and Kae. FRS2 was negatively regulated by miR-6873-3p in HUVECs. Conclusion Kae alleviated ox-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs by regulating circNOL12/miR-6873-3p/FRS2 axis.
Databáze: OpenAIRE
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