Transforming Growth Factor Beta (TGF-β1) Induces Pro-Reparative Phenotypic Changes in Epicardial Cells in Mice.

We evaluated the content of active form of TGF-β1 in the intact and post-infarction heart and the effect of this factor on the properties of epicardial cells. During the acute stage after myocardial infarction, the production of TGF-β1 in the heart increased, which closely correlated with activation of epicardial cells (appearance of a pool of Wt1+ epicardial cells entering the epithelial-mesenchymal transition). The role of TGF-β1 as the factor of epicardial activation was confirmed by the results of in vitro experiments: addition of recombinant TGF-β1 to cultured epicardial cells led to enhanced expression of genes of epithelial-mesenchymal transition and phenotypic transformation of these cells leading to the appearance of cells with markers of smooth muscle cells and fibroblasts. Our findings suggest that the regulatory axis "TGF-β1-epicardium cells" can be considered as an important link of the post-infarction reparative process and adaptive response during heart remodeling after myocardial infarction and as the target for therapeutic interventions.