A1 Refereed original research article in a scientific journal
Myostatin/activin blocking combined with exercise reconditions skeletal muscle expression profile of mdx mice
Authors: Kainulainen H, Papaioannou KG, Silvennoinen M, Autio R, Saarela J, Oliveira BM, Nyqvist M, Pasternack A, 't Hoen PAC, Kujala UM, Ritvos O, Hulmi JJ
Publisher: ELSEVIER IRELAND LTD
Publication year: 2015
Journal:: Molecular and Cellular Endocrinology
Journal name in source: MOLECULAR AND CELLULAR ENDOCRINOLOGY
Journal acronym: MOL CELL ENDOCRINOL
Volume: 399
Issue: C
First page : 131
Last page: 142
Number of pages: 12
ISSN: 0303-7207
eISSN: 1872-8057
DOI: https://doi.org/10.1016/j.mce.2014.10.001
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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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