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.

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, 1-15 [10.1038/srep23479].

Hedgehog associated to microparticles inhibits adipocyte differentiation via a non-canonical pathway

TADDEI, MAURIZIO;PETRICCI, ELENA;MANETTI, FABRIZIO;
2016-01-01

Abstract

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.
2016
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, 1-15 [10.1038/srep23479].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/991044