1. Protective Effect of miR-204 on Doxorubicin-Induced Cardiomyocyte Injury via HMGB1.
- Author
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Du Y, Liu G, Zhao L, and Yao R
- Subjects
- Animals, Apoptosis genetics, Cardiotoxins pharmacology, Doxorubicin pharmacology, HMGB1 Protein genetics, Inflammation chemically induced, Inflammation genetics, Inflammation metabolism, Inflammation prevention & control, Male, Mice, MicroRNAs genetics, Myocytes, Cardiac pathology, Apoptosis drug effects, Cardiotoxins adverse effects, Doxorubicin adverse effects, HMGB1 Protein metabolism, MicroRNAs metabolism, Myocytes, Cardiac metabolism
- Abstract
The toxicity of doxorubicin (DOX) limits its clinical application. Nevertheless, at present, there is no effective drug to prevent DOX-induced cardiac injury. miR-204 is a newly discovered miRNA with many protective effects on cardiovascular diseases. However, little research has been done on the effects of miR-204 on DOX-induced cardiac injury. Our study is aimed at investigating the effect of miR-204 on DOX-induced myocardial injury. An adenoassociated virus system was used to achieve cardiac-specific overexpression of miR-204. Two weeks later, the mice were intraperitoneally injected with DOX (15 mg/kg) to induce cardiac injury. H9c2 myocardial cells were used to validate the role of miR-204 in vitro. Our study showed that miR-204 expression was decreased in DOX-treated hearts. miR-204 overexpression improved cardiac function and alleviated cardiac inflammation, apoptosis, and autophagy induced by DOX. In addition, our results showed that miR-204 prevented DOX-induced injury in cardiomyocytes by directly decreasing HMGB1 expression. Moreover, the overexpression of HMGB1 could offset the protective effects of miR-204 against DOX-induced cardiac injury. In summary, our study showed that miR-204 protected against DOX-induced cardiac injury via the inhibition of HMGB1, and increasing miR-204 expression may be a new treatment option for patients with DOX-induced cardiac injury., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Youyou Du et al.)
- Published
- 2020
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