MiR-122敲低通过增强FOXO3表达调节血管平滑肌细胞表型转换。

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY Canadian journal of physiology and pharmacology Pub Date : 2023-12-01 Epub Date: 2023-09-25 DOI:10.1139/cjpp-2022-0549
Lan Zhang, Qian-Wei Huang, Yan-Fen Pu, Xiao-Qiang Xiao, Bian-Jing Song, Xue-Ping Zhang, Yong-Sheng Yang, Yu-Song Zhang, Fu-Han Gong
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摘要

血管平滑肌细胞(VSMCs)表型转换被鉴定为VSMCs的去分化、增殖和迁移能力增强,其中微小RNA被鉴定为该过程的重要调节因子。本研究旨在探讨miR-122对VSMC表型调节的病理生理作用。在此,结果显示,在接受血小板衍生生长因子BB(PDGF-BB)治疗的VSMCs中发现miR-122表达降低。接下来,我们研究了PDGF-BB刺激VSMCs中miR-122敲低的反应。MiR-122沉默表现出增加的增殖和迁移能力,而减弱分化标志物的表达。miR-122过表达逆转了上述结果。最后,我们进一步证明FOXO3是miR-122的重要靶点。总之,我们证明miR-122沉默部分通过上调FOXO3表达促进VSMC表型调节,这表明miR-122可能是新生内膜形成的新治疗靶点。
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MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

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来源期刊
CiteScore
4.00
自引率
4.80%
发文量
90
审稿时长
3-8 weeks
期刊介绍: Published since 1929, the Canadian Journal of Physiology and Pharmacology is a monthly journal that reports current research in all aspects of physiology, nutrition, pharmacology, and toxicology, contributed by recognized experts and scientists. It publishes symposium reviews and award lectures and occasionally dedicates entire issues or portions of issues to subjects of special interest to its international readership. The journal periodically publishes a “Made In Canada” special section that features invited review articles from internationally recognized scientists who have received some of their training in Canada.
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