Chemerin regulates normal angiogenesis and hypoxia-driven neovascularization
2022
Ben Dhaou, Cyrine | Mandi, Kamel | Frye, Mickaël | Acheampong, Angela | Radi, Ayoub | de Becker, Benjamin | Antoine, Mathieu | Baeyens, Nicolas | Wittamer, Valérie | Parmentier, Marc | Université libre de Bruxelles (ULB) | Physiologie de la reproduction et des comportements [Nouzilly] (PRC) ; Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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Show more [+] Less [-]English. Chemerin is a multifunctional protein initially characterized in our laboratory as a chemoattractant factor for leukocyte populations. Its main functional receptor is CMKLR1. We identified previously chemerin as an anti-tumoral factor inhibiting the vascularization of tumor grafts. We show here that overexpression of bioactive chemerin in mice results in a reduction of the density of the retinal vascular network during its development and in adults. Chemerin did not affect vascular sprouting during the post-natal development of the network, but rather promoted endothelial cell apoptosis and vessel pruning. This phenotype was reversed to normal in CMKLR1-deficient mice, demonstrating the role of this receptor. Chemerin inhibited also neoangiogenesis in a model of pathological proliferative retinopathy, and in response to hind-limb ischemia. Mechanistically, PTEN and FOXO1 antagonists could almost completely restore the density of the retinal vasculature, suggesting the involvement of the PI3-kinase/AKT pathway in the chemerin-induced vessel regression process.
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