Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis
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, a...
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doaj-55bd8d9c0a204ba49538bbaeb696d7962021-07-15T04:26:57ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-05-01137111419Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axisShuangzhan Li0Meihua Hao1Taisheng Wu2Zixuan Wang3Xicheng Wang4Junjian Zhang5Lei Zhang6Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, ChinaDepartment of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, ChinaDepartment of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, ChinaDepartment of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, ChinaDepartment of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, ChinaDepartment of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, ChinaCorrespondence to: Department of Cardiology, Huaihe Hospital of Henan University, No. 8 Baobei Road, Gulou District, Kaifeng, 477500 Henan, China.; Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan, ChinaBackground: 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.http://www.sciencedirect.com/science/article/pii/S0753332221002043KaeOx-LDLCircNOL12MiR-6873-3pFRS2HUVECs |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuangzhan Li Meihua Hao Taisheng Wu Zixuan Wang Xicheng Wang Junjian Zhang Lei Zhang |
spellingShingle |
Shuangzhan Li Meihua Hao Taisheng Wu Zixuan Wang Xicheng Wang Junjian Zhang Lei Zhang Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis Biomedicine & Pharmacotherapy Kae Ox-LDL CircNOL12 MiR-6873-3p FRS2 HUVECs |
author_facet |
Shuangzhan Li Meihua Hao Taisheng Wu Zixuan Wang Xicheng Wang Junjian Zhang Lei Zhang |
author_sort |
Shuangzhan Li |
title |
Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis |
title_short |
Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis |
title_full |
Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis |
title_fullStr |
Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis |
title_full_unstemmed |
Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis |
title_sort |
kaempferol alleviates human endothelial cell injury through circnol12/mir-6873-3p/frs2 axis |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-05-01 |
description |
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. |
topic |
Kae Ox-LDL CircNOL12 MiR-6873-3p FRS2 HUVECs |
url |
http://www.sciencedirect.com/science/article/pii/S0753332221002043 |
work_keys_str_mv |
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