MicroRNA-223-3p inhibits vascular calcification and the osteogenic switch of vascular smooth muscle cells.
MicroRNA-223-3p inhibits vascular calcification and the osteogenic switch of vascular smooth muscle cells.
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MicroRNA-223-3p抑制血管钙化和血管平滑肌细胞的成骨转换
DOI：
10.1016/j.jbc.2021.100483
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
Han Y;Zhang J;Huang S;Cheng N;Zhang C;Li Y;Wang X;Liu J;You B;Du J
血管钙化是钙羟基磷灰石矿物在动脉壁的异位沉积，涉及血管平滑肌细胞（VSMCs）向成骨表型的转分化。然而，调节VSMC成骨开关的潜在分子机制仍不完全清楚。在这项研究中，我们研究了microRNAs（miRNAs）在血管钙化中的作用。miRNA-seq转录组分析将miR-223- 3 p鉴定为钙化小鼠睾丸中的候选miRNA。MiR-223- 3 p敲除在中膜和动脉粥样硬化血管钙化模型中均加重钙化。此外，RNA-seq转录组分析证实JAK-STAT和PPAR信号通路在中膜和动脉粥样硬化钙化动脉瘤中均上调。这些信号通路中的基因与来自miRNA数据库的miR-223- 3 p的预测靶基因重叠，我们确定信号转导和转录激活因子3（STAT 3）为血管钙化中miR-223- 3 p的潜在靶基因。体外实验表明，miR-223- 3 p阻断了白细胞介素-6（IL-6）/STAT 3信号通路，从而阻止了VSMCs的成骨转换和钙化。相反，STAT 3的过表达减弱了miR-223- 3 p的作用。综上所述，结果表明miR-223- 3 p通过调节IL-6/STAT 3信号转导介导的VSMC转分化抑制中膜和动脉粥样硬化血管钙化的保护作用。
Vascular calcification is the ectopic deposition of calcium hydroxyapatite minerals in arterial wall, which involves the transdifferentiation of vascular smooth muscle cells (VSMCs) toward an osteogenic phenotype. However, the underlying molecular mechanisms regulating the VSMC osteogenic switch remain incompletely understood. In this study, we examined the roles of microRNAs (miRNAs) in vascular calcification. miRNA-seq transcriptome analysis identified miR-223-3p as a candidate miRNA in calcified mouse aortas. MiR-223-3p knockout aggravated calcification in both medial and atherosclerotic vascular calcification models. Further, RNA-seq transcriptome analysis verified JAK-STAT and PPAR signaling pathways were upregulated in both medial and atherosclerotic calcified aortas. Overlapping genes in these signaling pathways with predicted target genes of miR-223-3p derived from miRNA databases, we identified signal transducer and activator of transcription 3 (STAT3) as a potential target gene of miR-223-3p in vascular calcification. In vitro experiments showed that miR-223-3p blocked interleukin-6 (IL-6)/STAT3 signaling, thereby preventing the osteogenic switch and calcification of VSMCs. In contrast, overexpression of STAT3 diminished the effect of miR-223-3p. Taken together, the results indicate a protective role of miR-223-3p that inhibits both medial and atherosclerotic vascular calcification by regulating IL-6/STAT3 signaling-mediated VSMC transdifferentiation.
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影响因子：
3.6
作者：
Mackenzie, N. C. W.;Staines, K. A.;Zhu, D.;Genever, P.;MacRae, V. E.
通讯作者：
MacRae, V. E.
影响因子：
15.9
作者：
Dorhoi, Anca;Iannaccone, Marco;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
血细胞和血管平滑肌细胞之间的内分泌遗传信号：MicroRNA-223 在平滑肌功能和动脉粥样硬化形成中的作用。
影响因子：
24
作者：
Shan, Zhen;Qin, Shanshan;Li, Wen;Wu, Weibin;Yang, Jian;Chu, Maoping;Li, Xiaokun;Huo, Yuqing;Schaer, Gary L.;Wang, Shenming;Zhang, Chunxiang
通讯作者：
Zhang, Chunxiang
影响因子：
12.7
作者：
Cantoni C;Cignarella F;Ghezzi L;Mikesell B;Bollman B;Berrien-Elliott MM;Ireland AR;Fehniger TA;Wu GF;Piccio L
通讯作者：
Piccio L
影响因子：
37.8
作者：
Aikawa E;Aikawa M;Libby P;Figueiredo JL;Rusanescu G;Iwamoto Y;Fukuda D;Kohler RH;Shi GP;Jaffer FA;Weissleder R
通讯作者：
Weissleder R