Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy

Kazuki Yuasa, Kazumasa Okubo, Masaki Yoda, Kinya Otsu, Yasuyuki Ishii, Masaya Nakamura, Yoshiki Itoh, Keisuke Horiuchi

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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.

Original languageEnglish
Article number9037
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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ASJC Scopus subject areas

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Cite this

Yuasa, K., Okubo, K., Yoda, M., Otsu, K., Ishii, Y., Nakamura, M., Itoh, Y., & Horiuchi, K. (2018). Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy. Scientific Reports, 8(1), [9037]. https://doi.org/10.1038/s41598-018-26632-w