miR-27a-3p Targets ATF3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells.
miR-27a-3p Targets ATF3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells.
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DOI：
10.1016/j.omtn.2020.09.030
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Kook H
中科院分区：
文献类型：
--
作者：
Choe N;Kwon DH;Ryu J;Shin S;Cho HJ;Joung H;Eom GH;Ahn Y;Park WJ;Nam KI;Kim YK;Kook H
血管钙化是钙在血管中的异位沉积，与各种代谢疾病和动脉粥样硬化相关，是与这些疾病相关的发病率和死亡率的独立预测因子。在此，我们报告了microRNA-27 a-3 p（miR-27 a-3 p）的减少导致血管平滑肌细胞中激活转录因子3（ATF 3）（一种新的成骨转录因子）的增加。以大鼠血管平滑肌细胞为研究对象，构建microRNA（miRNA）和mRNA微阵列，通过生物信息学分析，筛选出受miRNA调控的miRNA和mRNA。无机磷酸盐显著降低A10细胞中miR-27 a-3 p的表达。在给予维生素D3的小鼠睾丸中，转录水平也降低。miR-27 a-3 p模拟物减少钙沉积，而miR-27 a-3 p抑制剂增加钙沉积。在细胞血管钙化模型中，Atf 3 mRNA水平上调，miR-27 a-3 p减少Atf 3 mRNA和蛋白水平。Atf 3转染可恢复miR-27 a-3 p诱导的钙沉积减少。我们的研究结果表明，miR-27 a-3 p的减少可能有助于通过ATF 3的去抑制来发展血管钙化。血管钙化导致血管僵硬，从而对心血管系统造成继发性损害。microRNA miR-27 a-3 p的减少导致转录因子ATF 3的增加，这会诱导钙沉积。这种miR-27 a-3 p/ATF信号通路可能为血管钙化提供新的治疗靶点。
Vascular calcification, the ectopic deposition of calcium in blood vessels, develops in association with various metabolic diseases and atherosclerosis and is an independent predictor of morbidity and mortality associated with these diseases. Herein, we report that reduction of microRNA-27a-3p (miR-27a-3p) causes an increase in activating transcription factor 3 (ATF3), a novel osteogenic transcription factor, in vascular smooth muscle cells. Both microRNA (miRNA) and mRNA microarrays were performed with rat vascular smooth muscle cells, and reciprocally regulated pairs of miRNA and mRNA were selected after bioinformatics analysis. Inorganic phosphate significantly reduced the expression of miR-27a-3p in A10 cells. The transcript level was also reduced in vitamin D3-administered mouse aortas. miR-27a-3p mimic reduced calcium deposition, whereas miR-27a-3p inhibitor increased it. The Atf3 mRNA level was upregulated in a cellular vascular calcification model, and miR-27a-3p reduced the Atf3 mRNA and protein levels. Transfection with Atf3 could recover the miR-27a-3p-induced reduction of calcium deposition. Our results suggest that reduction of miR-27a-3p may contribute to the development of vascular calcification by de-repression of ATF3. Vascular calcification causes stiffness of blood vessels, which causes secondary damage to the cardiovascular system. A reduction in the microRNA miR-27a-3p leads to an increase in the transcription factor ATF3, which induces calcium deposition. This miR-27a-3p/ATF signaling pathway may provide a novel therapeutic target for vascular calcification.
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影响因子：
9
作者：
Golub, Ellis E.
通讯作者：
Golub, Ellis E.
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
10.8
作者：
Durham AL;Speer MY;Scatena M;Giachelli CM;Shanahan CM
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
13.2
作者：
Giachelli, CM;Jono, S;Morii, H
通讯作者：
Morii, H