FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry
| Autor: | Timothy J. Mohun, Rachel Sturny, Karim Mesbah, Saverio Bellusci, Francesca Rochais, Robert G. Kelly, Michael B. Bennett, Cho-Ming Chao |
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| Přispěvatelé: | Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Physiology [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Heart development Cardiac repair Mice Physiology (medical) Internal medicine medicine Myocyte Animals Myocytes Cardiac Receptor Cells Cultured Cell Proliferation FGF10 Cardiac myocyte Cell Cycle Forkhead Box Protein O3 Forkhead Transcription Factors Heart Cell cycle Cell biology stomatognathic diseases medicine.anatomical_structure Endocrinology Ventricle FOXO3 Cardiomyocyte proliferation Cardiology and Cardiovascular Medicine Fibroblast Growth Factor 10 Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Cardiovascular Research Cardiovascular Research, Oxford University Press (OUP), 2014, 104 (3), pp.432-42. ⟨10.1093/cvr/cvu232⟩ Cardiovascular Research, 2014, 104 (3), pp.432-42. ⟨10.1093/cvr/cvu232⟩ |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvu232⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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