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Nat Commun. 2018 Aug 2;9(1):3030. doi: 10.1038/s41467-018-05439-3.

JNK regulates muscle remodeling via myostatin/SMAD inhibition.

Author information

1
Research Division, Joslin Diabetes Center, Boston, 02215, MA, USA. sarah.lessard@joslin.harvard.edu.
2
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, 02215, MA, USA. sarah.lessard@joslin.harvard.edu.
3
Research Division, Joslin Diabetes Center, Boston, 02215, MA, USA.
4
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, 02215, MA, USA.
5
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01605, MA, USA.
6
Faculty of Health Sciences and Medicine, Bond University, Gold Coast, 4226, QLD, Australia.
7
School of Medical Science, RMIT University, Melbourne, 3000, Australia.
8
Massey University, Palmerston North, 4442, New Zealand.
9
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, 02111, MA, USA.
10
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, 01605, MA, USA.

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.

PMID:
30072727
PMCID:
PMC6072737
DOI:
10.1038/s41467-018-05439-3
[Indexed for MEDLINE]
Free PMC Article

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