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Mol Cell Endocrinol. 2015 Jan 5;399:131-42. doi: 10.1016/j.mce.2014.10.001. Epub 2014 Oct 7.

Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice.

Author information

1
Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
2
Department of Signal Processing, Tampere University of Technology, Korkeakoulunkatu 1, P.O. BOX 553, Tampere FI-33101, Finland.
3
Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, Turku FIN-20520, Finland.
4
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, Helsinki FIN-00014, Finland.
5
Department of Human Genetics, Leiden University Medical Center (LUMC), Postzone S-04-P, PO Box 9600, Leiden 2300 RC, The Netherlands.
6
Department of Health Sciences, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland.
7
Department of Biology of Physical Activity, Neuromuscular Research Center, University of Jyväskylä, Rautpohjankatu 8, P.O. Box 35, Jyväskylä FI-40014, Finland. Electronic address: juha.hulmi@jyu.fi.

Abstract

Duchenne muscular dystrophy is characterized by muscle wasting and decreased aerobic metabolism. Exercise and blocking of myostatin/activin signaling may independently or combined counteract muscle wasting and dystrophies. The effects of myostatin/activin blocking using soluble activin receptor-Fc (sActRIIB-Fc) administration and wheel running were tested alone or in combination for 7 weeks in dystrophic mdx mice. Expression microarray analysis revealed decreased aerobic metabolism in the gastrocnemius muscle of mdx mice compared to healthy mice. This was not due to reduced home-cage physical activity, and was further downregulated upon sActRIIB-Fc treatment in enlarged muscles. However, exercise activated pathways of aerobic metabolism and counteracted the negative effects of sActRIIB-Fc. Exercise and sActRIIB-Fc synergistically increased expression of major urinary protein, but exercise blocked sActRIIB-Fc induced phosphorylation of STAT5 in gastrocnemius muscle. In conclusion, exercise alone or in combination with myostatin/activin blocking corrects aerobic gene expression profiles of dystrophic muscle toward healthy wild type mice profiles.

KEYWORDS:

Muscle hypertrophy; Muscular dystrophy; Oxidative metabolism; Physical activity; mRNA profiling

PMID:
25304272
DOI:
10.1016/j.mce.2014.10.001
[Indexed for MEDLINE]

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