Heat Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy.
Heat Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy.
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DOI：
10.1038/s41598-017-17572-y
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发表时间：
2017-12-12
影响因子：
4.6
通讯作者：
Hayashi K
中科院分区：
文献类型：
--
作者：
Nagata Y;Yamagishi M;Konno T;Nakanishi C;Asano Y;Ito S;Nakajima Y;Seguchi O;Fujino N;Kawashiri MA;Takashima S;Kitakaze M;Hayashi K
扩张型心肌病（DCM）心力衰竭的发病机制可能部分是由于心肌中三磷酸腺苷（ATP）的失调。在这些条件下，由骨骼肌生长期间上调5（USMG 5）基因编码的胰岛素敏感组织中的糖尿病相关蛋白（DAPIT）在线粒体ATP合酶的能量产生中起着至关重要的作用。为了确定USMG 5是否与心力衰竭的发展有关，我们进行了临床和实验研究。基因芯片分析显示，USMG 5和利钠肽前体A在人类衰竭心肌中的表达水平呈正相关。当内源性z-usmg 5在斑马鱼中被破坏使用吗啉代（MO）寡核苷酸，心包囊和心房面积较大，心室缩短分数减少相比，在控制MO组。与对照组相比，z-usmg 5 MO组中利钠肽的表达水平上调。此外，微阵列分析显示，钙信号通路中的基因在z-usmg 5 MO组中下调。这些结果表明，DAPIT在与DCM相关的心力衰竭的发展中起着至关重要的作用，因此可能是心力衰竭的治疗靶点。
The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium. Under these conditions, diabetes-associated protein in insulin-sensitive tissue (DAPIT), which is encoded by the upregulated during skeletal muscle growth 5 (USMG5) gene, plays a crucial role in energy production by mitochondrial ATP synthase. To determine whether USMG5 is related to the development of heart failure, we performed clinical and experimental studies. Microarray analysis showed that the expression levels of USMG5 were positively correlated with those of natriuretic peptide precursor A in the human failed myocardium. When endogenous z-usmg5 in zebrafish was disrupted using morpholino (MO) oligonucleotides, the pericardial sac and atrial areas were larger and ventricular fractional shortening was reduced compared to in the control MO group. The expression levels of natriuretic peptides were upregulated in the z-usmg5 MO group compared to in controls. Further, microarray analysis revealed that genes in the calcium signalling pathway were downregulated in the z-usmg5 MO group. These results demonstrate that DAPIT plays a crucial role in the development of heart failure associated with DCM and thus may be a therapeutic target for heart failure.
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