Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase

Science. 2022 Jun 17;376(6599):1343-1347. doi: 10.1126/science.abn3027. Epub 2022 Jun 16.


Effective tissue repair after myocardial infarction entails a vigorous angiogenic response, guided by incompletely defined immune cell-endothelial cell interactions. We identify the monocyte- and macrophage-derived cytokine METRNL (meteorin-like) as a driver of postinfarction angiogenesis and high-affinity ligand for the stem cell factor receptor KIT (KIT receptor tyrosine kinase). METRNL mediated angiogenic effects in cultured human endothelial cells through KIT-dependent signaling pathways. In a mouse model of myocardial infarction, METRNL promoted infarct repair by selectively expanding the KIT-expressing endothelial cell population in the infarct border zone. Metrnl-deficient mice failed to mount this KIT-dependent angiogenic response and developed severe postinfarction heart failure. Our data establish METRNL as a KIT receptor ligand in the context of ischemic tissue repair.

MeSH terms

  • Adipokines*
  • Animals
  • Cells, Cultured
  • Cytokines* / genetics
  • Cytokines* / metabolism
  • Endothelial Cells / metabolism
  • Heart Failure / etiology
  • Heart Failure / genetics
  • Ligands
  • Macrophages / metabolism
  • Mice
  • Mice, Mutant Strains
  • Myocardial Infarction* / complications
  • Myocardial Infarction* / physiopathology
  • Neovascularization, Physiologic*
  • Nerve Growth Factors* / genetics
  • Nerve Growth Factors* / metabolism
  • Proto-Oncogene Proteins c-kit* / metabolism


  • Adipokines
  • Cytokines
  • Ligands
  • Metrnl protein, human
  • Nerve Growth Factors
  • cometin protein, mouse
  • Proto-Oncogene Proteins c-kit