Journal article
Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase
Science (American Association for the Advancement of Science), Vol.376(6599), pp.1343-1347
06/17/2022
DOI: 10.1126/science.abn3027
PMID: 35709278
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. The adult mammalian heart has limited regenerative capacity and heals by scar formation after myocardial infarction. Effective repair of the injured heart entails a vigorous angiogenic response that mitigates scarring and helps to preserve pump function. Reboll et al . identified the myeloid cell-derived cytokine meteorin-like (METRNL) protein as being a critical driver of postinfarction angiogenesis and a high-affinity ligand for the stem cell factor receptor KIT (see the Perspective by Srivastava). METRNL promotes infarct repair in mice by selectively expanding the KIT-expressing endothelial cell population in the infarct border zone. Failure to mount this KIT-dependent angiogenic response provokes severe postinfarction heart failure. METRNL provides a mechanism for activating endothelial KIT signaling after tissue injury. —BAP The cytokine meteorin-like (METRNL) functions as a high-affinity ligand for the stem cell factor receptor KIT in endothelial cells.
Details
- Title: Subtitle
- Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase
- Creators
- Marc R. Reboll - Medizinische Hochschule HannoverStefanie Klede - Medizinische Hochschule HannoverManuel H. Taft - Medizinische Hochschule HannoverChen-Leng Cai - Indiana University School of MedicineLoren J. Field - Indiana University – Purdue University IndianapolisKory J. Lavine - Washington University in St. LouisAndrew L. Koenig - Washington University in St. LouisJenni Fleischauer - Medizinische Hochschule HannoverJohann Meyer - Medizinische Hochschule HannoverAxel Schambach - Medizinische Hochschule HannoverHans W. Niessen - Amsterdam University Medical CentersMaike Kosanke - Medizinische Hochschule HannoverJoop van den Heuvel - Helmholtz Centre for Infection ResearchAndreas Pich - Medizinische Hochschule HannoverJohann Bauersachs - Medizinische Hochschule HannoverXuekun Wu - Medizinische Hochschule HannoverLinqun Zheng - Medizinische Hochschule HannoverYong Wang - Medizinische Hochschule HannoverMortimer Korf-Klingebiel - Medizinische Hochschule HannoverFelix Polten - Medizinische Hochschule HannoverKai C. Wollert - Medizinische Hochschule Hannover
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.376(6599), pp.1343-1347
- DOI
- 10.1126/science.abn3027
- PMID
- 35709278
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Number of pages
- 5
- Language
- English
- Date published
- 06/17/2022
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985161355002771
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