RRC ID 54005
著者 Yuasa K, Okubo K, Yoda M, Otsu K, Ishii Y, Nakamura M, Itoh Y, Horiuchi K.
タイトル Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy.
ジャーナル Sci Rep
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.
巻・号 8(1)
ページ 9037
公開日 2018-6-13
DOI 10.1038/s41598-018-26632-w
PII 10.1038/s41598-018-26632-w
PMID 29899565
PMC PMC5998077
MeSH Animals Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism* Cell Line Denervation Enzyme Inhibitors / pharmacology Humans Male Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors Mitogen-Activated Protein Kinase 14 / genetics Mitogen-Activated Protein Kinase 14 / metabolism* Molecular Targeted Therapy / methods Muscle, Skeletal / drug effects Muscle, Skeletal / enzymology* Muscle, Skeletal / pathology Muscular Atrophy / enzymology* Muscular Atrophy / pathology Muscular Atrophy / prevention & control Signal Transduction / drug effects Signal Transduction / genetics
IF 3.998
引用数 3
リソース情報
ヒト・動物細胞 C2C12(RCB0987)