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| Status |
Public on Jun 04, 2020 |
| Title |
Stimulation of glycolysis via the pyruvate dehydrogenase axis promotes cardiomyocyte proliferation after injury in adult zebrafish. |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac contractions. However, the role of metabolism in cardiomyocyte proliferation remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), specifically in tissues bordering the damaged area. We proceed to show that impaired glycolysis decreases the number of proliferating cardiomyocytes following cardiac injury. These observations are further supported by analyses using loss-of-function models for the metabolic regulators Pkm2a and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 and a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.
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| Overall design |
Mock and Pdk3 expressing samples (n=2)
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| |
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| Contributor(s) |
Fukuda R, Guenther S, Kuenne C |
| Citation(s) |
32648304 |
| |
| Submission date |
Mar 16, 2020 |
| Last update date |
Aug 10, 2020 |
| Contact name |
Stefan Günther |
| E-mail(s) |
stefan.guenther@mpi-bn.mpg.de
|
| Organization name |
MPI for heart and lung research
|
| Street address |
ludwigtr. 43
|
| City |
bad nauheim |
| ZIP/Postal code |
61231 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA612885 |
| SRA |
SRP253004 |
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