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.

Chemerin 是一种多功能蛋白质，最初在我们的实验室中被描述为白细胞群的化学吸引因子。其主要功能受体是CMKLR1。我们以前将凯莫瑞确定为抑制肿瘤移植物血管化的抗肿瘤因子。我们在这里表明，在小鼠体内过度表达生物活性凯莫瑞会导致视网膜血管网络在其发育过程中和成人中的密度降低。Chemerin在网络的出生后发育过程中不影响血管发芽，而是促进内皮细胞凋亡和血管修剪。这种表型在 CMKLR1 缺陷小鼠中逆转为正常，证明了这种受体的作用。Chemerin 还抑制病理性增殖性视网膜病模型中的新血管生成，以及对后肢缺血的反应。