Targeting connexin37 alters angiogenesis and arteriovenous differentiation in the developing mouse retina.

Détails

ID Serval
serval:BIB_79F060AF8AB9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Targeting connexin37 alters angiogenesis and arteriovenous differentiation in the developing mouse retina.
Périodique
FASEB journal
Auteur(s)
Hamard L., Santoro T., Allagnat F., Meda P., Nardelli-Haefliger D., Alonso F., Haefliger J.A.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Statut éditorial
Publié
Date de publication
06/2020
Peer-reviewed
Oui
Volume
34
Numéro
6
Pages
8234-8249
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Connexin37 (Cx37) forms intercellular channels between endothelial cells (EC), and contributes to coordinate the motor tone of vessels. We investigated the contribution of this protein during physiological angiogenesis. We show that, compared to WT littermates, mice lacking Cx37 (Cx37 <sup>-/-</sup> ) featured (i) a decreased extension of the superficial vascular plexus during the first 4 days after birth; (ii) an increased vascular density at the angiogenic front at P6, due to an increase in the proliferative rate of EC and in the sprouting of the venous compartment, as well as to a somewhat displaced position of tip cells; (iii) a decreased coverage of newly formed arteries and veins by mural cells; (iv) altered ERK-dependent endothelial cells proliferation through the EphB4 signaling pathway, which is involved in the specification of veins and arteries. In vitro studies documented that, in the absence of Cx37, human venous EC (HUVEC) released less platelet-derived growth factor (PDGF) and more Angiopoietin-2, two molecules involved in the recruitment of mural cells. Treatment of mice with DAPT, an inhibitor of the Notch pathway, decreased the expression of Cx37, and partially mimicked in WT retinas, the alterations observed in Cx37 <sup>-/-</sup> mice. Thus, Cx37 contributes to (i) the early angiogenesis of retina, by interacting with the Notch pathway; (ii) the growth and maturation of neo-vessels, by modulating tip, stalk, and mural cells; (iii) the regulation of arteriovenous specification, thus, representing a novel target for treatments of retina diseases.
Mots-clé
Animals, Cell Differentiation/physiology, Cell Proliferation/physiology, Cells, Cultured, Connexins/metabolism, Endothelial Cells/metabolism, Endothelial Cells/physiology, Endothelium, Vascular/metabolism, Endothelium, Vascular/physiology, Female, Human Umbilical Vein Endothelial Cells, Humans, Male, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic/physiology, Retina/metabolism, Retina/physiology, Signal Transduction/physiology, angiogenesis, connexin37, retina, vascular remodeling
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/04/2020 18:06
Dernière modification de la notice
27/01/2021 7:27
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