Interleukin 37 promotes angiogenesis through TGF-β signaling

Sci Rep. 2017 Jul 21;7(1):6113. doi: 10.1038/s41598-017-06124-z.


IL-37 is a novel pro-angiogenic cytokine that potently promotes endothelial cell activation and pathological angiogenesis in our previous study, but the mechanisms behind the pro-angiogenic effect of IL-37 are less well understood. Extending our observations, we found that TGF-β interacts with IL-37, and potently enhances the binding affinity of IL-37 to the ALK1 receptor complex, thus allowing IL-37 to signal through ALK1 to activate pro-angiogenic responses. We further show that TGF-β and ALK1 are required in IL-37 induced pro-angiogenic response in ECs and in the mouse model of Matrigel plug and oxygen-induced retinopathy. The result suggests that IL-37 induces pro-angiogenic responses through TGF-β, which may act as the bridging molecule that mediates IL-37 binding to the TGF-β receptor complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Interleukin-1 / metabolism*
  • Interleukin-1 / pharmacology
  • Mice
  • Neovascularization, Physiologic*
  • Protein Binding
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction* / drug effects
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism*


  • Biomarkers
  • IL37 protein, human
  • Interleukin-1
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta