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Published on: March 30, 2019
miRNA-576 Alleviates the Malignant Progression of Atherosclerosis through Downregulating KLF5
Jing Wang1, Lihui Zhang1, Ting Wang1
1Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Objective:
To elucidate the role of microRNA-576 (miRNA-576) in alleviating the deterioration of atherosclerosis (AS) through downregulating krüpple-like factor 5 (KLF5).
Materials And Methods:
The AS model in mice was first constructed. Body weight, inflammation degrees, blood lipid, and relative levels of KLF5, miRNA-576, caspase-3, and bcl-2 in AS mice and control mice were compared. Dual-luciferase reporter gene assay was performed to evaluate the binding between miRNA-576 and KLF5. RAW264.7 cells were treated with 200 mg/L ox-LDL for establishing in vitro high-fat model. Regulatory effects of miRNA-576/KLF5 on relative levels of β-catenin and inflammatory factors in RAW264.7 cells were explored.
Results:
Body weight was heavier in AS mice than in controls. Protein levels of KLF5 and caspase-3 were upregulated, while bcl-2 was downregulated in AS mice. In particular, protein level of KLF5 was highly expressed in aortic tissues of AS mice. TC and LDL increased, and HDL decreased in AS mice compared with controls. Inflammatory factor levels were markedly elevated in AS mice. KLF5 was verified to be the target gene binding miRNA-576. Overexpression of miRNA-576 downregulated KLF5, inflammatory factors, and β-catenin in ox-LDL-treated RAW264.7 cells. Regulatory effect of miRNA-576 on the release of inflammatory factors in RAW264.7 cells could be partially abolished by KLF5.
Conclusions:
miRNA-576 alleviates malignant progression of AS via downregulating KLF5.
Insights
MicroRNA-576 (miRNA-576) alleviates atherosclerosis (AS) by downregulating krüpple-like factor 5 (KLF5). This study demonstrates miRNA-576
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Gene Regulation
Background:
- Atherosclerosis (AS) is a chronic inflammatory disease characterized by plaque buildup in arteries.
- Krüpple-like factor 5 (KLF5) is implicated in AS pathogenesis.
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression and cellular processes relevant to AS.
Purpose of the Study:
- To investigate the role of microRNA-576 (miRNA-576) in mitigating AS progression.
- To determine if miRNA-576 exerts its effects by downregulating krüpple-like factor 5 (KLF5).
Main Methods:
- Construction of an AS mouse model and comparison with control groups.
- Assessment of body weight, lipid profiles, inflammation markers, and protein/gene expression (KLF5, miRNA-576, caspase-3, bcl-2).
- In vitro studies using RAW264.7 cells treated with ox-LDL to explore the regulatory interactions between miRNA-576, KLF5, β-catenin, and inflammatory factors, including dual-luciferase reporter assays.
Main Results:
- AS mice exhibited increased body weight, elevated total cholesterol (TC) and low-density lipoprotein (LDL), decreased high-density lipoprotein (HDL), and heightened inflammation compared to controls.
- KLF5 and caspase-3 protein levels were upregulated, while bcl-2 was downregulated in AS mice, with high KLF5 expression in aortic tissues.
- miRNA-576 was confirmed to target KLF5; its overexpression reduced KLF5, inflammatory factors, and β-catenin in ox-LDL-treated cells, an effect partially reversed by KLF5.
Conclusions:
- miRNA-576 plays a protective role in AS by downregulating KLF5.
- Targeting miRNA-576 may represent a therapeutic strategy for AS.
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