Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy.
Sci Rep
; 8(1): 9037, 2018 06 13.
Article
in En
| MEDLINE
| ID: mdl-29899565
ABSTRACT
The loss of skeletal muscle mass is a major cause of falls and fractures in the elderly, leading to compromised independence and a decrease in the quality of life. However, only a few therapeutic interventions leading to marginal clinical benefits in patients with this condition are currently available. Therefore, the demand to further understand the pathology of muscle atrophy and establish a treatment modality for patients with muscle atrophy is significant. p38α mitogen-activated protein kinase (p38α MAPK) is a ubiquitous signaling molecule that is implicated in various cellular functions, including cell proliferation, differentiation, and senescence. In the present study, we generated a mutant line in which p38α MAPK is specifically abrogated in muscle tissues. Compared with the control mice, these mutant mice are significantly resistant to denervation-induced muscle atrophy, suggesting that p38α MAPK positively regulates muscle atrophy. We also identified CAMK2B as a potential downstream target of p38α MAPK and found that the pharmacological inhibition of CAMK2B activity suppresses denervation-induced muscle atrophy. Altogether, our findings identify p38α MAPK as a novel regulator of muscle atrophy and suggest that the suppression of intracellular signaling mediated by p38α MAPK serves as a potential target for the treatment of muscle atrophy.
Full text:
1
Database:
MEDLINE
Main subject:
Muscular Atrophy
/
Muscle, Skeletal
/
Mitogen-Activated Protein Kinase 14
/
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Year:
2018
Type:
Article