Oncostatin M Is a Major Mediator of Cardiomyocyte Dedifferentiation and Remodeling

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• 作者：Thomas Kubin¹ ;   ; ⁵ ; Jochen Pö ; ling¹ ;   ; ² ;   ; ⁵ ; Sawa Kostin¹ ; Praveen Gajawada¹ ; Stefan Hein³ ; Wolfgang Rees² ; Astrid Wietelmann¹ ; Minoru Tanaka⁴ ; Holger Lö ; rchner¹ ; Silvia Schimanski¹ ; Marten Szibor¹ ; Henning Warnecke² ; Thomas Braun¹ ;   ; ^{thomas.braun@mpi-bn.mpg.de}
• 刊名：Cell Stem Cell
• 出版年：2011
• 出版时间：4 November 2011
• 年：2011
• 卷：9
• 期：5
• 页码：420-432
• 全文大小：3953 K

文摘

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.