miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of Nrf2 in Mice
Joint Authors
Wang, Zhiwei
Liu, Huagang
Hu, Zhipeng
Li, Luocheng
Hu, Xiaoping
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-03
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was closely involved in doxorubicin- (DOX-) induced cardiotoxicity.
MicroRNA-200a (miR-200a) could target Keap1 mRNA and promote degradation of Keap1 mRNA, resulting in Nrf2 activation.
However, the role of miR-200a in DOX-related cardiotoxicity remained unclear.
Our study is aimed at investigating the effect of miR-200a on DOX-induced cardiotoxicity in mice.
For cardiotropic expression, male mice received an injection of an adeno-associated virus 9 (AAV9) system carrying miR-200a or miR-scramble.
Four weeks later, mice received a single intraperitoneal injection of DOX at 15 mg/kg.
In our study, we found that miR-200a mRNA was the only microRNA that was significantly decreased in DOX-treated mice and H9c2 cells.
miR-200a supplementation blocked whole-body wasting and heart atrophy caused by acute DOX injection, decreased the levels of cardiac troponin I and the N-terminal probrain natriuretic peptide, and improved cardiac and adult cardiomyocyte contractile function.
Moreover, miR-200a reduced oxidative stress and cardiac apoptosis without affecting matrix metalloproteinase and inflammatory factors in mice with acute DOX injection.
miR-200a also attenuated DOX-induced oxidative injury and cell loss in vitro.
As expected, we found that miR-200a activated Nrf2 and Nrf2 deficiency abolished the protection provided by miR-200a supplementation in mice.
miR-200a also provided cardiac benefits in a chronic model of DOX-induced cardiotoxicity.
In conclusion, miR-200a protected against DOX-induced cardiotoxicity via activation of the Nrf2 signaling pathway.
Our data suggest that miR-200a may represent a new cardioprotective strategy against DOX-induced cardiotoxicity.
American Psychological Association (APA)
Hu, Xiaoping& Liu, Huagang& Wang, Zhiwei& Hu, Zhipeng& Li, Luocheng. 2019. miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of Nrf2 in Mice. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1202206
Modern Language Association (MLA)
Hu, Xiaoping…[et al.]. miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of Nrf2 in Mice. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1202206
American Medical Association (AMA)
Hu, Xiaoping& Liu, Huagang& Wang, Zhiwei& Hu, Zhipeng& Li, Luocheng. miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of Nrf2 in Mice. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1202206
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202206