miR579-3p is an inhibitory modulator of neointimal hyperplasia and transcription factors c-MYB and KLF4.
miR579-3p is an inhibitory modulator of neointimal hyperplasia and transcription factors c-MYB and KLF4.
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DOI：
10.1038/s41420-023-01364-7
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发表时间：
2023-02-22
影响因子：
7
通讯作者：
Kent, K. Craig
中科院分区：
文献类型：
--
作者：
Xie, Xiujie;Shirasu, Takuro;Li, Jing;Guo, Lian-Wang;Kent, K. Craig
新生内膜增生（IH）是一种常见的血管病理学，通常表现为支架内再狭窄和旁路静脉移植失败。平滑肌细胞（SMC）表型转换是IH的核心，两者都受到一些microRNA的调节，但miR 579 - 3 p的作用，一个很少研究的microRNA，是未知的。无偏生物信息学分析表明，miR 579 - 3 p在用不同pro-IH细胞因子处理的人原代SMC中被抑制。此外，miR 579 - 3 p被软件预测为靶向c-MYB和KLF 4-两种已知促进SMC表型转换的主转录因子。有趣的是，通过局部输注表达miR 579 - 3 p的慢病毒来治疗受伤的大鼠颈动脉，可以降低损伤后14天的IH。在培养的人SMC中，用miR 579 - 3 p转染抑制SMC表型转换，如增殖/迁移减少和SMC收缩蛋白增加所示。miR 579 - 3 p转染下调c-MYB和KLF 4，荧光素酶检测显示miR 579 - 3 p靶向c-MYB和KLF 4 mRNAs的3′ UTR。在体内，免疫组织化学显示，用miR 579 - 3 p慢病毒治疗损伤的大鼠动脉减少了c-MYB和KLF 4，并增加了SMC收缩蛋白。因此，本研究将miR 579 - 3 p鉴定为先前未识别的IH和SMC表型转换的小RNA抑制剂，涉及其靶向c-MYB和KLF 4。对miR 579 - 3 p的进一步研究可能为翻译提供机会，以开发缓解IH的新疗法。
Neointimal hyperplasia (IH) is a common vascular pathology that typically manifests in in-stent restenosis and bypass vein graft failure. Smooth muscle cell (SMC) phenotypic switching is central to IH, both regulated by some microRNAs, yet the role of miR579-3p, a scarcely studied microRNA, is not known. Unbiased bioinformatic analysis suggested that miR579-3p was repressed in human primary SMCs treated with different pro-IH cytokines. Moreover, miR579-3p was software-predicted to target both c-MYB and KLF4 − two master transcription factors known to promote SMC phenotypic switching. Interestingly, treating injured rat carotid arteries via local infusion of miR579-3p-expressing lentivirus reduced IH 14 days after injury. In cultured human SMCs, transfection with miR579-3p inhibited SMC phenotypic switching, as indicated by decreased proliferation/migration and increased SMC contractile proteins. miR579-3p transfection downregulated c-MYB and KLF4, and luciferase assays indicated miR579-3p’s targeting of the 3′UTRs of the c-MYB and KLF4 mRNAs. In vivo, immunohistochemistry showed that treatment of injured rat arteries with the miR579-3p lentivirus reduced c-MYB and KLF4 and increased SMC contractile proteins. Thus, this study identifies miR579-3p as a previously unrecognized small-RNA inhibitor of IH and SMC phenotypic switch involving its targeting of c-MYB and KLF4. Further studies on miR579-3p may provide an opportunity for translation to develop IH-mitigating new therapeutics.
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影响因子：
21.3
作者：
Hergenreider, Eduard;Heydt, Susanne;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
2.4
作者：
Bhaskaran M;Mohan M
通讯作者：
Mohan M
影响因子：
4.6
作者：
Barbier RH;McCrea EM;Lee KY;Strope JD;Risdon EN;Price DK;Chau CH;Figg WD
通讯作者：
Figg WD
影响因子：
5.3
作者：
Huang Y;Urabe G;Zhang M;Li J;Ozer HG;Wang B;Kent KC;Guo LW
通讯作者：
Guo LW
DOI：
10.1073/pnas.1607753113
发表时间：
2016-08-23
影响因子：
11.1
作者：
Fattore, Luigi;Mancini, Rita;Ciliberto, Gennaro
通讯作者：
Ciliberto, Gennaro