Sonic Hedgehog Therapy in a Mouse Model of Age-Associated Impairment of Skeletal Muscle Regeneration

Eleonora Gaetani, Roberto Pola, Andrea Piccioni, Ilaria Gatto, Mariangela Palladino, Igor Giarretta, Enrico Pola, Marcy Silver, Roy Smith, Lynn Hlatky

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review


Sonic hedgehog (Shh) is a morphogen regulating muscle development during embryogenesis. We have shown that the Shh pathway is postnatally recapitulated after injury and during regeneration of the adult skeletal muscle and regulates angiogenesis and myogenesis after muscle injury. Here, we demonstrate that in 18-month-old mice, there is a significant impairment of the upregulation of the Shh pathway that physiologically occurs in the young skeletal muscle after injury. Such impairment is even more pronounced in 24-month-old mice. In old animals, intramuscular therapy with a plasmid encoding the human Shh gene increases the regenerative capacities of the injured muscle, in terms of Myf5-positive cells, regenerating myofibers, and fibrosis. At the molecular level, Shh treatment increases the upregulation of the prototypical growth factors, insulin-like growth factor-1 and vascular endothelial growth factor. These data demonstrate that Shh increases regeneration after injury in the muscle of 24-month-old mice and suggest that the manipulation of the Shh pathway may be useful for the treatment of muscular diseases associated with aging.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
Numero di pagine8
Stato di pubblicazionePubblicato - 2013


  • SHH

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