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

6533b7d7fe1ef96bd1268fba

RESEARCH PRODUCT

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

Peter A C 'T Hoen Reija Autio Juha J. Hulmi Bernardo Moreira Soares Oliveira Heikki Kainulainen Janne Saarela Urho M. Kujala Mika Silvennoinen Konstantinos G. Papaioannou Olli Ritvos Miro Nyqvist Arja Pasternack

subject

muscular dystrophy medicine.medical_specialty Duchenne muscular dystrophy Activin Receptors Type II Recombinant Fusion Proteins physical activity Myostatin Biology ta3111 Biochemistry Muscle hypertrophy 03 medical and health sciences Gastrocnemius muscle Mice 0302 clinical medicine Endocrinology oxidative metabolism Internal medicine Physical Conditioning Animal Gene expression medicine STAT5 Transcription Factor Animals muscle hypertrophy Muscular dystrophy Phosphorylation ta315 Muscle Skeletal Molecular Biology Wasting 030304 developmental biology Inhibin-beta Subunits 0303 health sciences Physical activity Skeletal muscle Myostatin musculoskeletal system medicine.disease Muscular dystrophy mRNA profiling Endocrinology medicine.anatomical_structure biology.protein Mice Inbred mdx Oxidative metabolism Muscle hypertrophy medicine.symptom 030217 neurology & neurosurgery

description

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 seven 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 towards healthy wild type mice profiles. peerReviewed

year	journal	country	edition	language
2015-01-05

10.1016/j.mce.2014.10.001 http://hdl.handle.net/1887/100725