title: Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling.
abstract: Cardiomyocyte remodeling, which includes partial dedifferentiation of cardiomyocytes, is a process that occurs during both acute and chronic disease processes. Here, we demonstrate that oncostatin M (OSM) is a major mediator of cardiomyocyte dedifferentiation and remodeling during acute myocardial infarction (MI) and in chronic dilated cardiomyopathy (DCM). Patients suffering from DCM show a strong and lasting increase of OSM expression and signaling. OSM treatment induces dedifferentiation of cardiomyocytes and upregulation of stem cell markers and improves cardiac function after MI. Conversely, inhibition of OSM signaling suppresses cardiomyocyte remodeling after MI and in a mouse model of DCM, resulting in deterioration of heart function after MI but improvement of cardiac performance in DCM. We postulate that dedifferentiation of cardiomyocytes initially protects stressed hearts but fails to support cardiac structure and function upon continued activation. Manipulation of OSM signaling provides a means to control the differentiation state of cardiomyocytes and cellular plasticity.
authors: Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, Bad Nauheim, 61321, Germany.
authors: Thomas
authors: T
authors: Kubin
authors: Jochen
authors: J
authors: Pöling
authors: Sawa
authors: S
authors: Kostin
authors: Praveen
authors: P
authors: Gajawada
authors: Stefan
authors: S
authors: Hein
authors: Wolfgang
authors: W
authors: Rees
authors: Astrid
authors: A
authors: Wietelmann
authors: Minoru
authors: M
authors: Tanaka
authors: Holger
authors: H
authors: Lörchner
authors: Silvia
authors: S
authors: Schimanski
authors: Marten
authors: M
authors: Szibor
authors: Henning
authors: H
authors: Warnecke
authors: Thomas
authors: T
authors: Braun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D054337:Cell Dedifferentiation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests / Q000187:drug effects; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053683:Oncostatin M / Q000378:metabolism* / Q000494:pharmacology; D053681:Oncostatin M Receptor beta Subunit / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D053681:Oncostatin M Receptor beta Subunit; D053683:Oncostatin M; D004247:DNA