HOLLIER, Pierre-Louis; CHAPOULY, Candice; DIOP, Aissata; GUIMBAL, Sarah; CORNUAULT, Lauriane; GADEAU, Alain-Pierre; RENAULT, Marie-Ange

doi:10.1093/cvr/cvaa285

Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

CHAPOULY, Candice
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

DIOP, Aissata
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

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Article de revue

Ce document a été publié dans

Cardiovascular Research. 2021-11-01, vol. 117, n° 12, p. 2489-2501

Résumé en anglais

The therapeutic potential of Hedgehog (Hh) signalling agonists for vascular diseases is of growing interest. However, molecular and cellular mechanisms underlying the role of the Hh signalling in vascular biology remain poorly understood. The purpose of the present article is to clarify some conflicting literature data. With this goal, we have demonstrated that, unexpectedly, ectopically administered N-terminal Sonic Hh (N-Shh) and endogenous endothelial-derived Desert Hh (Dhh) induce opposite effects in endothelial cells (ECs). Notably, endothelial Dhh acts under its full-length soluble form (FL-Dhh) and activates Smoothened in ECs, while N-Shh inhibits it. At molecular level, N-Shh prevents FL-Dhh binding to Patched-1 (Ptch1) demonstrating that N-Shh acts as competitive antagonist to FL-Dhh. Besides, we found that even though FL-Hh ligands and N-Hh ligands all bind Ptch1, they induce distinct Ptch1 localization. Finally, we confirmed that in a pathophysiological setting, i.e. brain inflammation, astrocyte-derived N-Shh acts as a FL-Dhh antagonist. The present study highlights for the first time that FL-Dhh and N-Hh ligands have antagonistic properties especially in ECs.< Réduire

Mots clés en anglais

Animals

Astrocytes

Capillary Permeability

Cells

Cultured

Cerebral Cortex

Corneal Neovascularization

Encephalomyelitis

Autoimmune

Experimental

Endothelial Cells

Female

Hedgehog Proteins

Ligands

Male

Mice

Knockout

Neovascularization

Pathologic

Patched-1 Receptor

Protein Binding

Signal Transduction

Smoothened Receptor

URI

https://oskar-bordeaux.fr/handle/20.500.12278/124664

DOI

http://dx.doi.org/10.1093/cvr/cvaa285

Unités de recherche

Biologie des maladies cardiovasculaires (BMC) - UMR 1034

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Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability

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Résumé en anglais

Mots clés en anglais

URI

DOI

Unités de recherche