Key result
FGF10 regulates regional cardiomyocyte proliferation in the foetal heart through a FOXO3/p27(kip1) pathway and triggers cell-cycle re-entry in adult cardiomyocytes.
Why the study?
Does FGF10 promote cardiomyocyte proliferation and cell-cycle re-entry in foetal and adult mice?
Does FGF10 promote cardiomyocyte proliferation and cell-cycle re-entry in foetal and adult mice?
FGF10 promotes regional foetal cardiomyocyte proliferation and triggers cell-cycle re-entry in adult cardiomyocytes, highlighting it as a potential target for cardiac regeneration.
Answers are grounded in this paper and cite their sources.
FGF10 merits testing as a regenerative target in mammalian models; leaves open translation to human cardiac repair.
AIMS: Cardiomyocyte proliferation gradually declines during embryogenesis resulting in severely limited regenerative capacities in the adult heart. Understanding the developmental processes controlling cardiomyocyte proliferation may thus identify new therapeutic targets to modulate the cell-cycle activity of cardiomyocytes in the adult heart. This study aims to determine the mechanism by which fibroblast growth factor 10 (FGF10) controls foetal cardiomyocyte proliferation and to test the hypothesis that FGF10 promotes the proliferative capacity of adult cardiomyocytes. METHODS AND RESULTS: Analysis of Fgf10(-/-) hearts and primary cardiomyocyte cultures reveals that altered ventricular morphology is associated with impaired proliferation of right but not left-ventricular myocytes. Decreased FOXO3 phosphorylation associated with up-regulated p27(kip) (1) levels was observed specifically in the right ventricle of Fgf10(-/-) hearts. In addition, cell-type-specific expression analysis revealed that Fgf10 and its receptor, Fgfr2b, are expressed in cardiomyocytes and not cardiac fibroblasts, consistent with a cell-type autonomous role of FGF10 in regulating regional specific myocyte proliferation in the foetal heart. Furthermore, we demonstrate that in vivo overexpression of Fgf10 in adult mice promotes cardiomyocyte but not cardiac fibroblast cell-cycle re-entry. CONCLUSION: FGF10 regulates regional cardiomyocyte proliferation in the foetal heart through a FOXO3/p27(kip1) pathway. In addition, FGF10 triggers cell-cycle re-entry of adult cardiomyocytes and is thus a potential target for cardiac repair.
No takes yet. Share an insight, caveat, or question.
Rochais et al. (2014) studied Cardiomyocyte proliferation. FGF10 knockout and overexpression vs. Wild-type/control was evaluated on Cardiomyocyte proliferation and cell-cycle re-entry. FGF10 regulates regional cardiomyocyte proliferation in the foetal heart through a FOXO3/p27(kip1) pathway and triggers cell-cycle re-entry in adult cardiomyocytes.
Synapse has enriched 10 related papers. Consider them for comparative context: