The Janus face of OSM-mediated cardiomyocyte dedifferentiation during cardiac repair and disease.

Jochen Pöling, Praveen Gajawada, Holger Lörchner, Viktoria Polyakova, Marten Szibor, Thomas Böttger, Henning Warnecke, Thomas Kubin, Thomas Braun

Index: Cell Cycle 11(3) , 439-45, (2012)

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Abstract

Dedifferentiation is a common phenomenon among plants but has only been found rarely in vertebrates where it is mostly associated with regenerative responses such as formation of blastemae in amphibians to initiate replacement of lost body parts. Relatively little attention has been paid to dedifferentiation processes in mammals although a decline of differentiated functions and acquisition of immature, "embryonic" properties is seen in various disease processes. Dedifferentiation of parenchymal cells in mammals might serve multiple purposes including (1) facilitation of tissue regeneration by generation of progenitor-like cells and (2) protection of cells from hypoxia by reduction of ATP consumption due to changes in energy metabolism and/or inactivation of energy-intensive "specialized" functions. We recently found that an inflammatory cytokine of the interleukin 6 family, oncostatin M (OSM), initiates dedifferentiation of cardiomyocytes both in vitro and in vivo. Interestingly, activation of the OSM signaling pathway protects the heart from acute myocardial ischemia but has a negative impact when continuously activated thereby promoting dilative cardiomyopathy. The strong presence of the OSM receptor on cardiomyocytes and the unique features of the OSM signaling circuit suggest a major role of OSM for cardiac protection and repair. We propose that continuous activation or malfunctions of the cellular dedifferentiation machinery might contribute to different disease conditions.