抑制miR-143-3p通过限制线粒体介导的细胞凋亡减轻心肌缺血再灌注损伤。

IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chuang-Hong Lu, De-Xin Chen, Kun Dong, Yun-Jiao Wu, Na Na, Hong Wen, Yao-Shi Hu, Yuan-Ying Liang, Si-Yi Wu, Bei-You Lin, Feng Huang, Zhi-Yu Zeng
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引用次数: 1

摘要

MicroRNA (miR)-143-3p是心肌缺血再灌注损伤(MI/RI)的潜在调控分子,其表达和病理作用一直存在争议。因此,我们建立了小鼠MI/RI和细胞缺氧/再氧化(H/R)模型来阐明miR-143-3p在MI/RI中的作用。心肌缺血30min后,小鼠再灌注3、6、12、24 h,再灌注后缺血心脏组织中miR-143-3p随时间升高。转染miR-143-3p的心肌细胞更容易发生凋亡。在机制上,miR-143-3p靶向B细胞淋巴瘤2 (bcl-2)。miR-143-3p抑制可减少H/R时心肌细胞凋亡,而特异性bcl-2抑制剂ABT-737可逆转。值得注意的是,miR-143-3p抑制上调bcl-2,使线粒体膜电位更好(Δψm),减少细胞质细胞色素c (cyto-c)和caspase蛋白,并使I/R小鼠的梗死面积最小化。总之,抑制miR-143-3p可能通过靶向bcl-2限制线粒体介导的细胞凋亡来缓解MI/RI。据我们所知,本研究进一步阐明了miR-143-3p在MI/RI早期的病理作用,抑制miR-143-3p可能是缺血性心肌疾病的有效治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition of miR-143-3p alleviates myocardial ischemia reperfusion injury via limiting mitochondria-mediated apoptosis.

MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (H/R) models were built for clarifying the miR-143-3p's role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (bcl-2). And miR-143-3p inhibition reduced cardiomyocytes apoptosis upon H/R, whereas it was reversed by a specific bcl-2 inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting bcl-2 to limit mitochondria-mediated apoptosis. To our knowledge, this study further clarifies the miR-143-3p's pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.

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来源期刊
Biological Chemistry
Biological Chemistry 生物-生化与分子生物学
CiteScore
7.20
自引率
0.00%
发文量
63
审稿时长
4-8 weeks
期刊介绍: Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences. Papers are published in a "Just Accepted" format within approx.72 hours of acceptance.
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