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Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Manfred Richter, Victoria Polyakova, Praveen Gajawada, Jochen Pöling, Henning Warnecke, Thomas Braun, Thomas Walther and Thomas Kubin

Background: It is well-known that elevated levels of Fibroblast Growth Factor-23 (FGF23), a bone derived hormone, in circulation are associated with renal failure. Recent studies emphasize the correlation between Heart Failure (HF) and FGF23, but the ability of cardiomyocytes themselves to express and secrete this phosphatonin is yet unknown. A further factor involved in HF is the cytokine oncostatin M (OSM). The aims of our study were: 1) to analyze the myocardium of HF patients in terms of FGF23 expression in cardiomyocytes and 2) to assess whether OSM is able to induce FGF23 production in cardiomyocytes.
Methods: Cultures of adult cardiomyocytes were treated with OSM and screened for the expression of FGF23 transcripts. FGF23 secretion was determined by Western blot and ELISA of cell culture supernatants. Heart explants of HF patients with Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM) and myocarditis (Myo) were analyzed by immunofluorescence using FGF23 antibodies and compared with healthy controls. FGF23 levels were also determined in mice with a cardiac restricted overexpression of Monocyte Chemotactic Protein-1 (MCP1), which developed an “inflammatory” Heart Failure (iHF) due to macrophage infiltration.
Results: OSM massively induced the expression and secretion of FGF23 in cultured adult cardiomyocytes. Confocal microscopy revealed high amounts of FGF23 positive cardiomyocytes in the myocardium of patients with ischemic heart disease (IHD), myocarditis, dilated cardiomyopathy (DCM) and in mice with iHF.
Conclusions: The presence of FGF23 in the myocardium of patients with different types of HF and in mice with “inflammatory” HF suggests that macrophages are responsible for the FGF23 expression in cardiomyocytes via OSM. Whether FGF23 acts as a regeneration promoting factor and/or potentially serves as a HF/transplantation marker has to be clarified.