| RRC ID |
66157
|
| 著者 |
Nijholt KT, Meems LMG, Ruifrok WPT, Maass AH, Yurista SR, Pavez-Giani MG, Mahmoud B, Wolters AHG, van Veldhuisen DJ, van Gilst WH, Silljé HHW, de Boer RA, Westenbrink BD.
|
| タイトル |
The erythropoietin receptor expressed in skeletal muscle is essential for mitochondrial biogenesis and physiological exercise.
|
| ジャーナル |
Pflugers Arch
|
| Abstract |
Erythropoietin (EPO) is a haematopoietic hormone that regulates erythropoiesis, but the EPO-receptor (EpoR) is also expressed in non-haematopoietic tissues. Stimulation of the EpoR in cardiac and skeletal muscle provides protection from various forms of pathological stress, but its relevance for normal muscle physiology remains unclear. We aimed to determine the contribution of the tissue-specific EpoR to exercise-induced remodelling of cardiac and skeletal muscle. Baseline phenotyping was performed on left ventricle and m. gastrocnemius of mice that only express the EpoR in haematopoietic tissues (EpoR-tKO). Subsequently, mice were caged in the presence or absence of a running wheel for 4 weeks and exercise performance, cardiac function and histological and molecular markers for physiological adaptation were assessed. While gross morphology of both muscles was normal in EpoR-tKO mice, mitochondrial content in skeletal muscle was decreased by 50%, associated with similar reductions in mitochondrial biogenesis, while mitophagy was unaltered. When subjected to exercise, EpoR-tKO mice ran slower and covered less distance than wild-type (WT) mice (5.5 ± 0.6 vs. 8.0 ± 0.4 km/day, p < 0.01). The impaired exercise performance was paralleled by reductions in myocyte growth and angiogenesis in both muscle types. Our findings indicate that the endogenous EPO-EpoR system controls mitochondrial biogenesis in skeletal muscle. The reductions in mitochondrial content were associated with reduced exercise capacity in response to voluntary exercise, supporting a critical role for the extra-haematopoietic EpoR in exercise performance.
|
| 巻・号 |
473(8)
|
| ページ |
1301-1313
|
| 公開日 |
2021-8-1
|
| DOI |
10.1007/s00424-021-02577-4
|
| PII |
10.1007/s00424-021-02577-4
|
| PMID |
34142210
|
| PMC |
PMC8302562
|
| MeSH |
Adaptation, Physiological*
Animals
Cardiomegaly, Exercise-Induced
Male
Mice, Knockout
Muscle, Skeletal / metabolism*
Myocardium / metabolism*
Neovascularization, Physiologic
Organelle Biogenesis*
Physical Conditioning, Animal / physiology*
Receptors, Erythropoietin / metabolism*
|
| IF |
3.158
|
| リソース情報 |
| 実験動物マウス |
RBRC00985 |
