Inhibition of miR-128-3p Attenuated Doxorubicin-Triggered Acute Cardiac Injury in Mice by the Regulation of PPAR-γ.

IF 3.5 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

PPAR Research Pub Date : 2021-04-20 eCollection Date: 2021-01-01 DOI:10.1155/2021/7595374

Wen-Bin Zhang, Yong-Fa Zheng, Yao-Gui Wu

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引用次数: 8

Abstract

Background: The clinical usefulness of doxorubicin (DOX), an anthracycline with antitumor activity, is limited by its cardiotoxicity. Oxidative stress and myocardial apoptosis were closely associated with DOX-induced cardiac dysfunction. It has been reported that microRNA-128-3p (miR-128-3p) was involved into the regulation of redox balance. However, the role of miR-128-3p in DOX-related cardiac injury remains not yet understood. The aim of this study was to investigate the biological effect of miR-128-3p in DOX-induced cardiotoxicity.

Methods: To induce DOX-related acute cardiac injury, mice were subjected to a single injection of DOX. Inhibition of myocardial miR-128-3p was achieved by an adeno-associated virus (AAV9) system carrying a miR-128-3p sponge.

Results: The data in our study indicated that miR-128-3p was upregulated in DOX-treated hearts and cardiomyocytes. Inhibition of miR-128-3p attenuated DOX-related cardiac injury and improved cardiac function in mice. Moreover, miR-128-3p inhibition could suppress myocardial inflammatory response, oxidative damage, and cell apoptotic death in DOX-treated mice. Further analysis showed that miR-128-3p could directly target peroxisome proliferator-activated receptor γ (PPAR-γ) and decrease PPAR-γ expression. Moreover, the protective effects provided by miR-128-3p inhibition were abolished by a PPAR-γ antagonist in vivo and in vitro.

Conclusions: miR-128-3p inhibition attenuated DOX-related acute cardiac injury via the regulation of PPAR-γ in mice.

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PPAR-γ调控miR-128-3p减弱阿霉素引发的小鼠急性心脏损伤

背景:阿霉素(DOX)是一种具有抗肿瘤活性的蒽环类药物，其临床应用受到心脏毒性的限制。氧化应激和心肌凋亡与dox诱导的心功能障碍密切相关。有报道称，microRNA-128-3p (miR-128-3p)参与了氧化还原平衡的调控。然而，miR-128-3p在dox相关心脏损伤中的作用尚不清楚。本研究的目的是探讨miR-128-3p在dox诱导的心脏毒性中的生物学作用。方法:小鼠单次注射DOX诱导DOX相关性急性心脏损伤。心肌miR-128-3p的抑制是通过携带miR-128-3p海绵的腺相关病毒(AAV9)系统实现的。结果:我们的研究数据表明，miR-128-3p在dox处理的心脏和心肌细胞中上调。抑制miR-128-3p可减轻小鼠dox相关的心脏损伤并改善心功能。此外，抑制miR-128-3p可以抑制dox处理小鼠的心肌炎症反应、氧化损伤和细胞凋亡。进一步分析表明，miR-128-3p可以直接靶向过氧化物酶体增殖物激活受体γ (PPAR-γ)，并降低PPAR-γ的表达。此外，在体内和体外，miR-128-3p抑制所提供的保护作用被PPAR-γ拮抗剂所消除。结论:miR-128-3p抑制通过调节小鼠PPAR-γ减轻dox相关的急性心脏损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.20

自引率

3.40%

发文量

审稿时长

12 months

期刊介绍： PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.