Postnatal recapitulation of embryonic hedgehog pathway in response to skeletal XXXX .

@entity1 @entity63 @entity7 @entity32356 @entity4851 @entity2750
BACKGROUND: Hedgehog (Hh) proteins are morphogens regulating epithelial-mesenchymal signaling during several crucial processes of embryonic development, including muscle patterning. Sonic ( @entity4851 ), Indian (Ihh), and Desert ( @entity32356 ) hedgehog constitute the repertoire of Hh genes in @entity1 . The activities of all 3 are transduced via the Patched ( @entity2750 ) receptor. Recent observations indicate that exogenous administration of @entity4851 induces angiogenesis. Here, we studied whether the endogenous Hh pathway, in addition to its functions during embryogenesis, plays a physiological role in muscle regeneration after @entity63 in adults. METHODS AND RESULTS: We found that skeletal @entity63 induces strong local upregulation of @entity4851 mRNA and protein. In addition, the @entity2750 receptor is activated in interstitial mesenchymal cells within the @entity63 area, indicating that these cells respond to @entity4851 and that the @entity4851 pathway is functional. We also found that @entity4851 -responding cells produce @entity7 under @entity63 conditions and that systemic treatment with a @entity4851 -blocking antibody inhibits the local angiogenic response and the upregulation of @entity7 . CONCLUSIONS: Our study shows that the Hh signaling may be recapitulated postnatally in adult and fully differentiated muscular tissues and has a regulatory role on angiogenesis during muscle regeneration after @entity63 . These findings demonstrate a novel biological activity for the Hh pathway with both fundamental and potential therapeutic implications.
