Functional and morphological recovery of dystrophic muscles in mice treated with deacetylase inhibitors.
Pharmacological interventions that increase myofiber size counter the functional decline of dystrophic muscles. We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)-deficient mice by inducing the expression of the myostatin antagonist follistatin in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic muscles resistance to contraction-coupled degeneration and alleviated both morphological and functional consequences of the primary genetic defect. These results provide a rationale for using deacetylase inhibitors in the pharmacological therapy of muscular dystrophies.
Minetti
G C
GC
Dulbecco Telethon Institute at Fondazione A. Cesalpino, Institute of Cell Biology and Tissue Engineering, San Raffaele Biomedical Science Park of Rome, Via Castel Romano 100, 00128, Rome, Italy.
Colussi
C
C
Adami
R
R
Serra
C
C
Mozzetta
C
C
Parente
V
V
Fortuni
S
S
Straino
S
S
Sampaolesi
M
M
Di Padova
M
M
Illi
B
B
Gallinari
P
P
Steinkühler
C
C
Capogrossi
M C
MC
Sartorelli
V
V
Bottinelli
R
R
Gaetano
C
C
Puri
P L
PL
D000818:Animals; D016189:Dystrophin / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis / Q000473:pathology; D038681:Follistatin / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009132:Muscles / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010654:Phenylbutyrates / Q000494:pharmacology; D049031:Sarcoglycans / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000201:enzymology; D014635:Valproic Acid / Q000494:pharmacology
D016189:Dystrophin; D004791:Enzyme Inhibitors; D038681:Follistatin; D006877:Hydroxamic Acids; D010654:Phenylbutyrates; D049031:Sarcoglycans; C012589:trichostatin A; D014635:Valproic Acid