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: Thomas Kubin, Jochen Pöling, Sawa Kostin, Praveen Gajawada, Stefan Hein, Wolfgang Rees, Astrid Wietelmann, Minoru Tanaka, Holger Lörchner, Silvia Schimanski, Marten Szibor, Henning Warnecke, Thomas Braun
• Journal: Cell stem cell (Cell Stem Cell) Vol. 9 Issue 5 Pg. 420-32 (Nov 04 2011) ISSN: 1875-9777 [Electronic] United States
• PMID: 22056139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Cardiotonic Agents
• Oncostatin M Receptor beta Subunit
• Oncostatin M
• DNA

Topics

• Animals
• Biomarkers (metabolism)
• Blotting, Western
• Cardiomyopathy, Dilated (metabolism, physiopathology)
• Cardiotonic Agents (metabolism)
• Cell Cycle (drug effects)
• Cell Dedifferentiation (drug effects)
• DNA (biosynthesis)
• Fluorescent Antibody Technique
• Gene Deletion
• Gene Expression Regulation (drug effects)
• Heart Function Tests (drug effects)
• Humans
• Mice
• Mice, Transgenic
• Myocardial Infarction (metabolism, pathology, physiopathology)
• Myocardium (pathology)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Oncostatin M (metabolism, pharmacology)
• Oncostatin M Receptor beta Subunit (metabolism)
• Rats
• Signal Transduction (drug effects, genetics)
• Stem Cells (cytology, drug effects, metabolism)
• Ventricular Remodeling (drug effects, physiology)