Hedgehog (Hh) is a critical regulator of adipogenesis. Extracellular vesicles are natural Hh carriers, as illustrated by activated/apoptotic lymphocytes specifically shedding microparticles (MP) bearing the morphogen (MP Hh+). We show that MP Hh+ inhibit adipocyte differentiation and orientate mesenchymal stem cells towards a pro-osteogenic program. Despite a Smoothened (Smo)-dependency, MP Hh+ anti-adipogenic effects do not activate a canonical Hh signalling pathway in contrast to those elicited either by the Smo agonist SAG or recombinant Sonic Hedgehog. The Smo agonist GSA-10 recapitulates many of the hallmarks of MP Hh+ anti-adipogenic effects. The adipogenesis blockade induced by MP Hh+ and GSA-10 was abolished by the Smo antagonist LDE225. We further elucidate a Smo/Lkb1/Ampk axis as the non-canonical Hh pathway used by MP Hh+ and GSA-10 to inhibit adipocyte differentiation. Our results highlight for the first time the ability of Hh-enriched MP to signal via a non-canonical pathway opening new perspectives to modulate fat development.
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|Titolo:||Hedgehog associated to microparticles inhibits adipocyte differentiation via a non-canonical pathway|
|Citazione:||Fleury, A., Hoch, L., Martinez, M.C., Faure, H., Taddei, M., Petricci, E., et al. (2016). Hedgehog associated to microparticles inhibits adipocyte differentiation via a non-canonical pathway. SCIENTIFIC REPORTS, 6, 23479.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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