Targeting connexin37 alters angiogenesis and arteriovenous differentiation in the developing mouse retina
| Autor: | Lauriane Hamard, Denise Nardelli-Haefliger, Paolo Meda, Tania Santoro, Florent Allagnat, Florian Alonso, Jacques-Antoine Haefliger |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Angiogenesis medicine.medical_treatment Notch signaling pathway Neovascularization Physiologic Biochemistry Connexins Retina Mural cell Mice 03 medical and health sciences 0302 clinical medicine Human Umbilical Vein Endothelial Cells Genetics medicine Animals Humans Molecular Biology Cells Cultured Cell Proliferation biology Chemistry Growth factor Endothelial Cells Cell Differentiation In vitro Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure cardiovascular system biology.protein Female Endothelium Vascular Signal transduction 030217 neurology & neurosurgery Platelet-derived growth factor receptor Signal Transduction Biotechnology |
| Zdroj: | The FASEB Journal. 34:8234-8249 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.202000257r |
| Popis: | 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 -/- ) 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 -/- 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. |
| Databáze: | OpenAIRE |
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