In mammals, cardiomyocyte proliferation decreases rapidly after birth resulting in limited regenerative capacities in the adult heart. Deciphering developmental mechanisms controlling cardiomyocyte proliferation may thus identify new therapeutic targets to promote adult cardiomyocyte cell cycle re-entry and therefore, cardiac regeneration. We recently uncovered a role for the Fibroblast Growth Factor 10 (FGF10) signalling in regulating both fetal and adult cardiomyocyte proliferation.

Our study aims to characterize the role of FGF10 in pathological conditions and to determine the relevance of FGF10 as a potential target for heart regeneration.

We used an experimental mouse model of Myocardial Infarction (MI), together with FGF10 gain and loss of function mouse models.

We first showed that MI leads to increased FGF10 expression levels in cardiomyocytes of the injured ventricle suggesting a potential role for FGF10 in pathological conditions. Adult transgenic mice with reduced FGF10 expression were subjected to MI. Our results revealed that while reduced FGF10 expression has no impact on cardiomyocyte hypertrophy and apoptosis, it significantly impairs cardiomyocyte proliferative capacities and exacerbates cardiac fibrosis infiltration post-MI. Moreover, reduced FGF10 expression leads to a worsened cardiac function and remodelling post-MI, strongly demonstrating the protective role of FGF10 in pathological conditions. To evaluate FGF10 regenerative capacities, conditional overexpression of FGF10 was achieved in adult mice subjected to MI. By promoting cardiomyocyte proliferation and preventing cardiac fibrosis infiltration, increased FGF10 expression levels post-MI preserves cardiac remodelling and function.

Altogether, this study thus identifies FGF10 as a potential target to improve the limited innate regenerative capacities of the myocardium after injury, of direct clinical relevance for heart regeneration.