WELBIO and I.R.I.B.H.M, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, B-1070, Brussels, Belgium.
Physiologie de la Reproduction et des Comportements, University of Tours, INRA Val-de-Loire UMR-85, CNRS UMR-1247, Tours, France.
Angiogenesis. 2022 May;25(2):159-179. doi: 10.1007/s10456-021-09818-1. Epub 2021 Sep 15.
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.
趋化素是一种多功能蛋白，最初在我们实验室中被鉴定为白细胞群体的趋化因子。其主要功能受体是 CMKLR1。我们之前已经确定趋化素是一种抗肿瘤因子，可抑制肿瘤移植物的血管生成。我们在这里表明，在小鼠中过表达生物活性趋化素会导致其发育过程中和成年期视网膜血管网络密度降低。趋化素在网络的出生后发育过程中并不影响血管发芽，而是促进内皮细胞凋亡和血管修剪。在 CMKLR1 缺陷型小鼠中，这种表型被逆转至正常，表明该受体的作用。趋化素还抑制病理性增殖性视网膜病变模型和后肢缺血模型中的新生血管形成。从机制上讲，PTEN 和 FOXO1 拮抗剂几乎可以完全恢复视网膜血管的密度，表明 PI3-激酶/AKT 途径参与了趋化素诱导的血管退化过程。
