MiR-411-5p Promotes Vascular Smooth Muscle Cell Phenotype Switch by Inhibiting Expression of Calmodulin Regulated Spectrin-Associated Protein-1

IF 1.2 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Yong Qiao, Dong Wang, Gaoliang Yan, Zhanneng Yang, Chengchun Tang
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Abstract

When stimulated, vascular smooth muscle cells (VSMCs) change from a differentiated to a dedifferentiated phenotype. Dedifferentiated VSMCs have a key activity in cardiovascular diseases such as in-stent restenosis. MicroRNAs (miRNAs) have crucial functions in conversion of differentiated VSMCs to a dedifferentiated phenotype. We investigated the activity of miR-411-5p in the proliferation, migration, and phenotype switch of rat VSMCs.

Based on a microRNA array assay, miR-411-5p expression was found to be significantly increased in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB). A CCK-8 assay, transwell assay, and scratch test were performed to measure the effect of miR-411-5p on the proliferation and migration of PDGF-BB-treated VSMCs. MiR-411-5p promoted expression of dedifferentiated phenotype markers such as osteopontin and tropomyosin 4 in PDGF-BB-treated VSMCs. Using mimics and inhibitors, we identified the target of miR-411-5p in PDGF-BB-treated VSMCs and found that calmodulin-regulated spectrin-associated protein-1 (CAMSAP1) was involved in the phenotypic switch mediated by PDGF-BB.

By inhibiting expression of CAMSAP1, miR-411-5p enhanced the proliferation, migration, and phenotype switch of VSMCs.

Blockade of miR-411-5p interaction with CAMSAP1 is a promising approach to treat in-stent restenosis.

MiR-411-5p 通过抑制钙调蛋白调控谱联蛋白-1 的表达促进血管平滑肌细胞表型转换
当受到刺激时,血管平滑肌细胞(VSMC)会从分化表型转变为去分化表型。脱分化的血管平滑肌细胞在支架内再狭窄等心血管疾病中具有关键活性。微小 RNA(miRNA)在分化型 VSMC 转换为去分化型表型的过程中具有关键作用。我们研究了 miR-411-5p 在大鼠血管内皮细胞增殖、迁移和表型转换中的活性。基于 microRNA 阵列检测,我们发现在血小板衍生生长因子-BB(PDGF-BB)刺激下培养的血管内皮细胞中,miR-411-5p 的表达显著增加。研究人员采用 CCK-8 试验、Transwell 试验和划痕试验来测定 miR-411-5p 对经 PDGF-BB 处理的 VSMC 增殖和迁移的影响。MiR-411-5p 促进了 PDGF-BB 处理的 VSMCs 中骨桥蛋白和肌球蛋白 4 等去分化表型标志物的表达。利用模拟物和抑制剂,我们确定了 miR-411-5p 在 PDGF-BB 处理的 VSMCs 中的靶点,并发现钙调蛋白调节的谱蛋白相关蛋白-1(CAMSAP1)参与了 PDGF-BB 介导的表型转换。通过抑制 CAMSAP1 的表达,miR-411-5p 增强了 VSMC 的增殖、迁移和表型转换。
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
International heart journal
International heart journal 医学-心血管系统
CiteScore
2.50
自引率
6.70%
发文量
148
审稿时长
6-12 weeks
期刊介绍: Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.
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