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

Research output: Contribution to journalArticle

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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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Muscular Atrophy
Denervation
p38 Mitogen-Activated Protein Kinases
Cell Aging
Cell Differentiation
Skeletal Muscle
Therapeutics
Quality of Life
Cell Proliferation
Pharmacology
Pathology
Muscles

ASJC Scopus subject areas

  • General

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Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy. / Yuasa, Kazuki; Okubo, Kazumasa; Yoda, Masaki; Otsu, Kinya; Ishii, Yasuyuki; Nakamura, Masaya; Itoh, Yoshiki; Horiuchi, Keisuke.

In: Scientific Reports, Vol. 8, No. 1, 9037, 01.12.2018.

Research output: Contribution to journalArticle

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, vol. 8, no. 1, 9037. https://doi.org/10.1038/s41598-018-26632-w
Yuasa, Kazuki ; Okubo, Kazumasa ; Yoda, Masaki ; Otsu, Kinya ; Ishii, Yasuyuki ; Nakamura, Masaya ; Itoh, Yoshiki ; Horiuchi, Keisuke. / Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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