| RRC ID |
81358
|
| Author |
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.
|
| Title |
Heat Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy.
|
| Journal |
Sci Rep
|
| Abstract |
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.
|
| Volume |
7(1)
|
| Pages |
17417
|
| Published |
2017-12-12
|
| DOI |
10.1038/s41598-017-17572-y
|
| PII |
10.1038/s41598-017-17572-y
|
| PMID |
29234032
|
| PMC |
PMC5727169
|
| MeSH |
Animals
Atrial Natriuretic Factor / metabolism
Cardiomyopathy, Dilated / metabolism*
Cardiomyopathy, Dilated / pathology
Gene Expression
Gene Knockdown Techniques
Heart Failure / metabolism
Heart Failure / pathology
Humans
Mitochondrial Proton-Translocating ATPases / genetics
Mitochondrial Proton-Translocating ATPases / metabolism*
Mitochondrial Proton-Translocating ATPases / physiology
Myocardium / metabolism
Myocardium / pathology
Zebrafish
Zebrafish Proteins / genetics
Zebrafish Proteins / physiology*
|
| IF |
3.998
|
| Resource |
| Zebrafish |
hspGFF3A |
