Oncostatin M Is a Major Mediator of Cardiomyocyte Dedifferentiation and Remodeling

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 i...

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Bibliographic Details
Published in:Cell stem cell 2011-11, Vol.9 (5), p.420-432
Main Authors: Kubin, Thomas, Pöling, Jochen, Kostin, Sawa, Gajawada, Praveen, Hein, Stefan, Rees, Wolfgang, Wietelmann, Astrid, Tanaka, Minoru, Lörchner, Holger, Schimanski, Silvia, Szibor, Marten, Warnecke, Henning, Braun, Thomas
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biomarkers - metabolism
Blotting, Western
Cardiomyopathy, Dilated - metabolism
Cardiomyopathy, Dilated - physiopathology
Cardiotonic Agents - metabolism
Cell Cycle - drug effects
Cell Dedifferentiation - drug effects
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
DNA - biosynthesis
Fluorescent Antibody Technique
Fundamental and applied biological sciences. Psychology
Gene Deletion
Gene Expression Regulation - drug effects
Heart Function Tests - drug effects
Humans
Mice
Mice, Transgenic
Molecular and cellular biology
Myocardial Infarction - metabolism
Myocardial Infarction - pathology
Myocardial Infarction - physiopathology
Myocardium - pathology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Oncostatin M - metabolism
Oncostatin M - pharmacology
Oncostatin M Receptor beta Subunit - metabolism
Rats
Signal Transduction - drug effects
Signal Transduction - genetics
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
Ventricular Remodeling - drug effects
Ventricular Remodeling - physiology
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Summary: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. ► Oncostatin M induces dedifferentiation of cardiomyocytes in vitro and in vivo via Oβ ► OSM induces progenitor cell markers in cardiomyocytes in vitro and in vivo ► OSM-mediated dedifferentiation protects the myocardium after cardiac infarction ► Extended dedifferentiation of cardiomyocytes by OSM impairs cardiac function
ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2011.08.013