Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling.
Deficiency of miR-409-3p improves myocardial neovascularization and function through modulation of DNAJB9/p38 MAPK signaling.
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DOI：
10.1016/j.omtn.2023.05.021
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发表时间：
2023-06-13
期刊：
影响因子：
--
通讯作者：
Icli, Basak
中科院分区：
文献类型：
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作者：
Bestepe, Furkan;Fritsche, Colette;Lakhotiya, Kartik;Niosi, Carolyn E.;Ghanem, George F.;Martin, Gregory L.;Pal-Ghosh, Ruma;Becker-Greene, Dakota;Weston, James;Hollan, Ivana;Risnes, Ivar;Rynning, Stein Erik;Solheim, Liv Heidi;Feinberg, Mark W.;Blanton, Robert M.;Icli, Basak
血管生成对于心肌梗死（MI）后的组织修复至关重要，心肌梗死在胰岛素抵抗或糖尿病下会加剧。microRNA是血管生成的调节因子。我们研究了miR-409- 3 p在梗死后血管生成中的代谢调节。miR-409- 3 p在急性冠状动脉综合征（ACS）患者和急性MI小鼠模型中增加。在内皮细胞（EC）中，棕榈酸可诱导miR-409- 3 p的表达，而血管内皮生长因子（VEGF）和成纤维细胞生长因子（FGF）可降低其表达。miR-409- 3 p的过表达在棕榈酸存在下降低EC增殖和迁移，而抑制则具有相反的效果。EC中的RNA测序（RNA-seq）分析鉴定DNAJ同源物亚家族B成员9（DNAJB 9）为miR-409- 3 p的靶标。过表达miR-409- 3 p使DNAJB 9 mRNA和蛋白表达分别降低47%和31%，而Argonaute 2微核糖核蛋白免疫沉淀后，DNAJB 9 mRNA增加1.9倍。这些作用通过p38丝裂原活化蛋白激酶（MAPK）介导。EC特异性miR-409- 3 p敲除（KO）小鼠（miR-409 ECKO）的缺血再灌注（I/R）损伤增加了isolectin B4（53.3%）、CD 31（56%）和DNAJB 9（41.5%）。与对照小鼠相比，miR-409 ECKO中的左心室射血分数（EF）提高了28%，梗死面积减少了33.8%。这些发现支持miR-409- 3 p在心肌缺血的血管生成EC反应中的重要作用。Istanbul及其同事研究了miR-409- 3 p在内皮细胞中的代谢调节，以及它如何调节急性心肌梗死后的血管生成。小鼠中miR-409- 3 p的内皮细胞特异性遗传缺失改善了响应于心肌缺血的血管生成和心脏功能，并靶向DNAJB 9/p38丝裂原活化蛋白激酶（MAPK）信号通路。
Angiogenesis is critical for tissue repair following myocardial infarction (MI), which is exacerbated under insulin resistance or diabetes. MicroRNAs are regulators of angiogenesis. We examined the metabolic regulation of miR-409-3p in post-infarct angiogenesis. miR-409-3p was increased in patients with acute coronary syndrome (ACS) and in a mouse model of acute MI. In endothelial cells (ECs), miR-409-3p was induced by palmitate, while vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) decreased its expression. Overexpression of miR-409-3p decreased EC proliferation and migration in the presence of palmitate, whereas inhibition had the opposite effects. RNA sequencing (RNA-seq) profiling in ECs identified DNAJ homolog subfamily B member 9 (DNAJB9) as a target of miR-409-3p. Overexpression of miR-409-3p decreased DNAJB9 mRNA and protein expression by 47% and 31% respectively, while enriching DNAJB9 mRNA by 1.9-fold after Argonaute2 microribonucleoprotein immunoprecipitation. These effects were mediated through p38 mitogen-activated protein kinase (MAPK). Ischemia-reperfusion (I/R) injury in EC-specific miR-409-3p knockout (KO) mice (miR-409ECKO) fed a high-fat, high-sucrose diet increased isolectin B4 (53.3%), CD31 (56%), and DNAJB9 (41.5%). The left ventricular ejection fraction (EF) was improved by 28%, and the infarct area was decreased by 33.8% in miR-409ECKO compared with control mice. These findings support an important role of miR-409-3p in the angiogenic EC response to myocardial ischemia. Icli and colleagues examined the metabolic regulation of miR-409-3p in endothelial cells and how it regulates angiogenesis following acute myocardial infarction. Endothelial cell-specific genetic deletion of miR-409-3p in mice improves angiogenesis and heart function in response to myocardial ischemia and targets the DNAJB9/p38 mitogen-activated protein kinase (MAPK) signaling pathway.
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影响因子：
11.2
作者：
Dong D;Stapleton C;Luo B;Xiong S;Ye W;Zhang Y;Jhaveri N;Zhu G;Ye R;Liu Z;Bruhn KW;Craft N;Groshen S;Hofman FM;Lee AS
通讯作者：
Lee AS
DOI：
10.1152/ajpheart.00583.2005
发表时间：
2006-01-01
影响因子：
4.8
作者：
Greer, JJM;Ware, DP;Lefer, DJ
通讯作者：
Lefer, DJ
影响因子：
5.4
作者：
Gu, Xuemei;Wang, Xiao-Qian;Shen, Fei-Xia
通讯作者：
Shen, Fei-Xia
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.
影响因子：
3.3
作者：
Ibanez, Borja;James, Stefan;Widimsky, Petr
通讯作者：
Widimsky, Petr