JNK regulates muscle remodeling via myostatin/SMAD inhibition

Sarah J Lessard, Tara L MacDonald, Prerana Pathak, Myoung Sook Han, Vernon G Coffey, Johann Edge, Donato A Rivas, Michael F Hirshman, Roger J Davis, Laurie J Goodyear

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Abstract

Skeletal muscle has a remarkable plasticity to adapt and remodel in response to environmental cues, such as physical exercise. Endurance exercise stimulates improvements in muscle oxidative capacity, while resistance exercise induces muscle growth. Here we show that the c-Jun N-terminal kinase (JNK) is a molecular switch that when active, stimulates muscle fibers to grow, resulting in increased muscle mass. Conversely, when muscle JNK activation is suppressed, an alternative remodeling program is initiated, resulting in smaller, more oxidative muscle fibers, and enhanced aerobic fitness. When muscle is exposed to mechanical stress, JNK initiates muscle growth via phosphorylation of the transcription factor, SMAD2, at specific linker region residues leading to inhibition of the growth suppressor, myostatin. In human skeletal muscle, this JNK/SMAD signaling axis is activated by resistance exercise, but not endurance exercise. We conclude that JNK acts as a key mediator of muscle remodeling during exercise via regulation of myostatin/SMAD signaling.
Original languageEnglish
Article number3030
Number of pages14
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 2 Aug 2018

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Myostatin
JNK Mitogen-Activated Protein Kinases
muscles
physical exercise
Muscle
Muscles
muscle fibers
skeletal muscle
endurance
suppressors
Skeletal Muscle
phosphorylation
Growth
fitness
cues
Durability
Inhibition (Psychology)
plastic properties
Mechanical Stress
switches

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Lessard, S. J., MacDonald, T. L., Pathak, P., Han, M. S., Coffey, V. G., Edge, J., ... Goodyear, L. J. (2018). JNK regulates muscle remodeling via myostatin/SMAD inhibition. Nature Communications, 9(1), [3030 ]. https://doi.org/10.1038/s41467-018-05439-3
Lessard, Sarah J ; MacDonald, Tara L ; Pathak, Prerana ; Han, Myoung Sook ; Coffey, Vernon G ; Edge, Johann ; Rivas, Donato A ; Hirshman, Michael F ; Davis, Roger J ; Goodyear, Laurie J. / JNK regulates muscle remodeling via myostatin/SMAD inhibition. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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Lessard, SJ, MacDonald, TL, Pathak, P, Han, MS, Coffey, VG, Edge, J, Rivas, DA, Hirshman, MF, Davis, RJ & Goodyear, LJ 2018, 'JNK regulates muscle remodeling via myostatin/SMAD inhibition' Nature Communications, vol. 9, no. 1, 3030 . https://doi.org/10.1038/s41467-018-05439-3

JNK regulates muscle remodeling via myostatin/SMAD inhibition. / Lessard, Sarah J; MacDonald, Tara L; Pathak, Prerana; Han, Myoung Sook; Coffey, Vernon G; Edge, Johann; Rivas, Donato A; Hirshman, Michael F; Davis, Roger J; Goodyear, Laurie J.

In: Nature Communications, Vol. 9, No. 1, 3030 , 02.08.2018.

Research output: Contribution to journalArticleResearchpeer-review

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