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

Marc R. Reboll, Stefanie Klede, Manuel H. Taft, Chen-Leng Cai, Loren J. Field, Kory J. Lavine, Andrew L. Koenig, Jenni Fleischauer, Johann Meyer, Axel Schambach, Hans W. Niessen, Maike Kosanke, Joop van den Heuvel, Andreas Pich, Johann Bauersachs, Xuekun Wu, Linqun Zheng, Yong Wang, Mortimer Korf-Klingebiel, Felix PoltenKai C. Wollert

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1343-1347
Number of pages5
JournalScience
Volume376
Issue number6599
DOIs
Publication statusPublished - 17 Jun 2022

Cite this