From the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (T.Y., Q.L., M.Z., Y.H., R.W., X.Z., G.X., J.Y., S.B.S.); Johns Hopkins University School of Medicine, Baltimore, MD (Q.L., X.Y.); State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China (Y.Y., J.J., H.Z., X.H., S.B.S., X.L.); Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China (G.L., P.L.); Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX (D.B.C.); and Department of Stomatology, Huashan Hospital, Fudan University, Shanghai, China (S.L.).
Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2638-46. doi: 10.1161/ATVBAHA.115.306543. Epub 2015 Oct 29.
Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Interleukin 37 (IL-37) is a newly identified cytokine of the IL-1 family, some members of which are important in inflammation and angiogenesis. However, the function of IL-37 in angiogenesis remains unknown. We aimed to explore the regulatory role of IL-37 in pathological and physiological angiogenesis.
We found that IL-37 was expressed and secreted in endothelial cells and upregulated under hypoxic conditions. IL-37 enhanced endothelial cell proliferation, capillary formation, migration, and vessel sprouting from aortic rings with potency comparable with that of vascular endothelial growth factor. IL-37 activates survival signals including extracellular signal-regulated kinase 1/2 and AKT in endothelial cells. IL-37 promoted vessel growth in implanted Matrigel plug in vivo in a dose-dependent manner with potency comparable with that of basic fibroblast growth factor. In the mouse model of retinal vascular development, neonatal mice administrated with IL-37 displayed increased neovascularization. We demonstrated further that IL-37 promoted pathological angiogenesis in the mouse model of oxygen-induced retinopathy.
Our findings suggest that IL-37 is a novel and potent proangiogenic cytokine with essential role in pathophy siological settings.
在病理生理环境中，血管生成受到生长因子和细胞因子的严密控制。白细胞介素 37（IL-37）是 IL-1 家族中新发现的一种细胞因子，其某些成员在炎症和血管生成中起重要作用。然而，IL-37 在血管生成中的功能尚不清楚。本研究旨在探讨 IL-37 在病理性和生理性血管生成中的调节作用。
我们发现，IL-37 在血管内皮细胞中表达和分泌，并在缺氧条件下上调。IL-37 增强内皮细胞的增殖、毛细血管形成、迁移和主动脉环中的血管发芽，其效力可与血管内皮生长因子相媲美。IL-37 在血管内皮细胞中激活包括细胞外信号调节激酶 1/2 和 AKT 在内的存活信号。IL-37 以剂量依赖性方式在体内植入的 Matrigel 塞中促进血管生长，其效力可与碱性成纤维细胞生长因子相媲美。在视网膜血管发育的小鼠模型中，给予 IL-37 的新生小鼠显示出新生血管增多。我们进一步证明，IL-37 促进了氧诱导性视网膜病变小鼠模型中的病理性血管生成。
我们的研究结果表明，IL-37 是一种新型的、有效的促血管生成细胞因子，在病理生理环境中具有重要作用。
