Sonic hedgehog mediates a novel pathway of PDGF-BB-dependent vessel maturation

Abstract : Recruitment of mural cells, i.e. pericytes and smooth muscle cells (SMCs), is essential to improve the maturation of newly formed vessels. Sonic hedgehog (Shh) has been suggested to promote the formation of larger and more muscularized vessels, but the underlying mechanisms of this process have not yet been elucidated. We first identified Shh as a target of PDGF-BB and found that SMCs respond to Shh by upregulating ERK1/2 and Akt phosphorylation. We next showed that PDGF-BB-induced SMC migration was reduced after inhibition of Shh or its signaling pathway. Moreover, we found that PDGF-BB-induced SMC migration, involves Shh-mediated motility. In vivo, in the mouse model of corneal angiogenesis, Shh is expressed by mural cells of newly formed blood vessels. PDGF-BB inhibition reduced Shh expression, demonstrating that Shh is a target of PDGF-BB, confirming in vitro experiments. Finally, we found that in vivo inhibition of either PDGF-BB or Shh signaling reduces NG2+ mural cell recruitment into neovessels and subsequently reduces neo-vessel lifespan. Our findings demonstrate, for the first time, that Shh is involved in PDGF-BB-induced SMC migration and recruitment of mural cells into neo-vessels and elucidate the molecular signaling pathway involved in this process.
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Article dans une revue
Blood, American Society of Hematology, 2014, pp.123(15)2429-2437
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Soumis le : mardi 2 juin 2015 - 15:12:39
Dernière modification le : mercredi 7 février 2018 - 14:52:06
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  • HAL Id : inserm-01159066, version 1
  • PUBMED : 24472833

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Qinyu Yao, Marie-Ange Renault, Candice Chapouly, Soizic Vandierdonck, Isabelle Belloc, et al.. Sonic hedgehog mediates a novel pathway of PDGF-BB-dependent vessel maturation. Blood, American Society of Hematology, 2014, pp.123(15)2429-2437. 〈inserm-01159066〉

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