miR‐381‐3p inhibits high glucose‐induced vascular smooth muscle cell proliferation and migration by targeting HMGB1
| Autor: | Feng Yang, Hanyun Zhou, Xiao-Shan Zhu, Hongshen Zhang, Kezhong Ma |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle Cell Survival Myocytes Smooth Muscle Apoptosis Inflammation medicine.disease_cause Muscle Smooth Vascular Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Cell Movement Drug Discovery Genetics medicine Humans HMGB1 Protein Molecular Biology Cells Cultured Genetics (clinical) Cell Proliferation TUNEL assay Cell growth Chemistry Transfection MicroRNAs Oxidative Stress Glucose 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Cancer research Molecular Medicine RNA Interference Tumor necrosis factor alpha medicine.symptom Reactive Oxygen Species Oxidative stress |
| Zdroj: | The Journal of Gene Medicine. 23 |
| ISSN: | 1521-2254 1099-498X |
| Popis: | Background Hyperglycemia increases the risk of many cardiovascular diseases (CVD), and the dysregulation of proliferation and migration in vascular smooth muscle cells (VSMCs) also participates in the pathogenesis of CVD. miR-381-3p is known to suppress the proliferation and migration of multiple human cell types. Nevertheless, the function of miR-381-3p in VSMCs remains largely indistinct. Methods A quantitative real-time polymerase chain reaction (qRT-PCR) was employed to investigate miR-381-3p expression in high-glucose-induced VSMCs. Inflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6, as well as oxidative stress markers SOD and MDA, were determined by an enzyme-linked immunosorbent assay. Reactive oxygen species generation was examined using a 2,7'-dichlorofluorescein kit. The proliferation, migration and apoptosis of VSMCs were monitored by 3-(4,5-dimethylthiazl2-yl)-2,5-diphenyltetazolium bromide (MTT), transwell and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays. The TargetScan database (http://www.targetscan.org) was employed to seek the potential target gene of miR-381-3p. Interaction between miR-381-3p and HMGB1 was determined by a qRT-PCR, western blotting and a luciferase reporter assay. Results miR-381-3p expression was significantly reduced in a VSMCs dysfunction model induced by high-glucose in a dose- and time-dependent manner. Transfection of miR-381-3p mimics suppressed the inflammation, oxidative stress, proliferation and migration of VSMCs, whereas apoptosis of VSMCs was promoted, and the transfection of miR-381-3p inhibitors had the opposite effect. Mechanistically, HMGB1, an important factor in inflammation response, was confirmed as a target gene of miR-381-3p. Conclusions miR-381-3p targets HMGB1 to suppress the inflammation, oxidative stress, proliferation and migration of high-glucose-induced VSMCs by targeting HMGB1. |
| Databáze: | OpenAIRE |
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