Nestin expression is dynamically regulated in cardiomyocytes during embryogenesis.
Nestin expression is dynamically regulated in cardiomyocytes during embryogenesis.
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在胚胎发生过程中，巢蛋白的表达在心肌细胞中动态调节。
DOI：
10.1002/jcp.26165
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发表时间：
2018-04
影响因子：
5.6
通讯作者：
Calderone A
中科院分区：
文献类型：
--
作者：
Hertig V;Matos-Nieves A;Garg V;Villeneuve L;Mamarbachi M;Caland L;Calderone A
在胚胎发育过程中，心肌细胞中中间丝蛋白巢蛋白的表达涉及的转录因子仍然不确定。在9.5 - 10.5天胚胎小鼠的心脏中，在心房和心室心肌细胞中检测到巢蛋白染色，并且亚群共表达Tbx 5。在发育的后期，心肌细胞中的巢蛋白免疫反应性逐渐减弱，并且在17，5天胚胎小鼠的心脏中不存在。在野生型11.5天胚胎小鼠的心脏中，54±7%的小梁表达巢蛋白，并且在Tbx 5 +/−和Gata 4 +/−胚胎的心脏中，该百分比显著增加。细胞周期蛋白Ki 67和转录辅激活因子雅普-1仍然普遍存在于Tbx 5 +/−和Gata 4 +/−胚胎小鼠心脏中鉴定的巢蛋白（+）-心肌细胞的细胞核中。佛波醇12，13-二丁酸酯处理新生大鼠心室心肌细胞增加了雅普-1磷酸化，并且共同施用p38 MAPK抑制剂SB 203580导致显著的去磷酸化。用维替泊芬拮抗去磷酸化雅普-1信号传导抑制佛波醇12，13-二丁酸酯/SB 203580介导的新生心肌细胞巢蛋白表达和BrdU掺入。用含有针对中间丝蛋白的shRNA的AAV 9去除巢蛋白显著减少了重新进入细胞周期的新生心肌细胞的数量。这些发现表明，Tbx 5和Gata 4依赖性事件负调控巢蛋白在胚胎发育过程中的心肌细胞的表达。相比之下，去磷酸化的雅普-1通过上调中间丝蛋白巢蛋白发挥作用，在心肌细胞的细胞周期重新进入中起着重要作用。基于这些数据，雅普-1的类似作用可能在Tbx 5 +/−和Gata 4 +/−小鼠的心脏中普遍存在。
The transcriptional factors implicated in the expression of the intermediate filament protein nestin in cardiomyocytes during embryogenesis remain undefined. In the heart of 9,5–10,5 day embryonic mice, nestin staining was detected in atrial and ventricular cardiomyocytes and a subpopulation co-expressed Tbx5. At later stages of development, nestin immunoreactivity in cardiomyocytes gradually diminished and was absent in the heart of 17,5 day embryonic mice. In the heart of wild type 11,5 day embryonic mice, 54±7% of the trabeculae expressed nestin and the percentage was significantly increased in the hearts of Tbx5+/− and Gata4+/− embryos. The cell cycle protein Ki67 and transcriptional coactivator Yap-1 were still prevalent in the nucleus of nestin(+)-cardiomyocytes identified in the heart of Tbx5+/− and Gata4+/− embryonic mice. Phorbol 12,13-dibutyrate treatment of neonatal rat ventricular cardiomyocytes increased Yap-1 phosphorylation and co-administration of the p38 MAPK inhibitor SB203580 led to significant dephosphorylation. Antagonism of dephosphorylated Yap-1 signalling with verteporfin inhibited phorbol 12,13-dibutyrate/SB203580-mediated nestin expression and BrdU incorporation of neonatal cardiomyocytes. Nestin depletion with an AAV9 containing a shRNA directed against the intermediate filament protein significantly reduced the number of neonatal cardiomyocytes that re-entered the cell cycle. These findings demonstrate that Tbx5- and Gata4-dependent events negatively regulate nestin expression in cardiomyocytes during embryogenesis. By contrast, dephosphorylated Yap-1 acting via upregulation of the intermediate filament protein nestin plays a seminal role in the cell cycle re-entry of cardiomyocytes. Based on these data, an analogous role of Yap-1 may be prevalent in the heart of Tbx5+/− and Gata4+/− mice.
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影响因子：
4.6
作者：
Heallen, Todd;Morikawa, Yuka;Martin, James F.
通讯作者：
Martin, James F.
DOI：
10.1038/nrd4161
发表时间：
2014-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.6
作者：
Beguin, Pauline C.;Gosselin, Hugues;Calderone, Angelino
通讯作者：
Calderone, Angelino
影响因子：
5.6
作者：
El-Helou, Vivianne;Chabot, Andreanne;Calderone, Angelino
通讯作者：
Calderone, Angelino
影响因子：
29.4
作者：
Gruber R;Panayiotou R;Nye E;Spencer-Dene B;Stamp G;Behrens A
通讯作者：
Behrens A