IL-37 Is a Novel Proangiogenic Factor of Developmental and Pathological Angiogenesis

Tianshu Yang, Qing Lin, Mengmeng Zhao, Yongguang Hu, Ying Yu, Jiayi Jin, Hongyan Zhou, Xiao Hu, Rongbin Wei, Xuetao Zhang, Xiaoping Yang, Gaoqin Liu, Peirong Lu, Guotong Xu, Jianhua Yang, David B. Corry, Shao Bo Su, Shangfeng Liu, Xialin Liu

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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. Approach and Results-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. Conclusions-Our findings suggest that IL-37 is a novel and potent proangiogenic cytokine with essential role in pathophy siological settings.

Original languageEnglish (US)
Pages (from-to)2638-2646
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume35
Issue number12
DOIs
StatePublished - Dec 1 2015

Keywords

  • Cytokines
  • endothelial cell
  • inflammation
  • interleukins
  • oxygen-induced retinopathy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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