Sonic Hedgehog Regulates Angiogenesis and Myogenesis During Post-Natal Skeletal Muscle Regeneration

Giuseppe Straface, Andrea Flex, Eleonora Gaetani, Federico Biscetti, Giovanni Pecorini, Enrico Pola, Flavia Angelini, Egidio Stigliano, Roberto Pola

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86 Citazioni (Scopus)


Sonic hedgehog (Shh) is a morphogen regulating crucial epithelial-mesenchymal interactions during embryonic development, but its signaling pathway is considered generally silent in post-natal life. In this study, we demonstrate that Shh is de novo expressed after injury and during regeneration of the adult skeletal muscle. Shh expression is followed by significant upregulation of its receptor and target gene Ptc1 in injured and regenerating muscles. The reactivation of the Shh signaling pathway has an important regulatory role on injury-induced angiogenesis, as inhibition of Shh function results in impaired upregulation of prototypical angiogenic agents, such as vascular endothelial growth factor (VEGF) and stromal-derived factor (SDF)-1alpha, decreased muscle blood flow, and reduced capillary density after injury. In addition, Shh reactivation plays a regulatory role on myogenesis, as its inhibition impairs the activation of the myogenic regulatory factors Myf-5 and MyoD, decreases the upregulation of insulin-like growth factor (IGF)-1, and reduces the number of myogenic satellite cells at injured site. Finally, Shh inhibition results in muscle fibrosis, increased inflammatory reaction, and compromised motor functional recovery after injury. These data demonstrate that the Shh pathway is functionally important for adult skeletal muscle regeneration and displays pleiotropic angiogenic and myogenic potentials in post-natal life. These findings might constitute the foundation for new therapeutic approaches for muscular diseases in humans.
Lingua originaleEnglish
pagine (da-a)2424-2435
Numero di pagine12
RivistaJournal of Cellular and Molecular Medicine
Stato di pubblicazionePubblicato - 2009


  • angiogenesis
  • myogenesis
  • regeneration
  • skeletal muscle
  • sonic hedgehog


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