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FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry

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dc.contributor.author Rochais F.
dc.contributor.author Sturny R.
dc.contributor.author Chao C.
dc.contributor.author Mesbah K.
dc.contributor.author Bennett M.
dc.contributor.author Mohun T.
dc.contributor.author Bellusci S.
dc.contributor.author Kelly R.
dc.date.accessioned 2018-09-18T20:02:33Z
dc.date.available 2018-09-18T20:02:33Z
dc.date.issued 2014
dc.identifier.issn 0008-6363
dc.identifier.uri https://dspace.kpfu.ru/xmlui/handle/net/136000
dc.description.abstract © The Author 2014. 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<sup>-/-</sup> 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<sup>kip1</sup> levelswas observed specifically in the right ventricle of Fgf10<sup>-/-</sup> 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<sup>kip1</sup> pathway. In addition, FGF10 triggers cell-cycle re-entry of adult cardiomyocytes and is thus a potential target for cardiac repair.
dc.relation.ispartofseries Cardiovascular Research
dc.subject Cardiac repair
dc.subject Cardiomyocyte proliferation
dc.subject Fibroblast growth factor 10
dc.subject Heart development
dc.title FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry
dc.type Article
dc.relation.ispartofseries-issue 3
dc.relation.ispartofseries-volume 104
dc.collection Публикации сотрудников КФУ
dc.relation.startpage 432
dc.source.id SCOPUS00086363-2014-104-3-SID84924857741


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  • Публикации сотрудников КФУ Scopus [24551]
    Коллекция содержит публикации сотрудников Казанского федерального (до 2010 года Казанского государственного) университета, проиндексированные в БД Scopus, начиная с 1970г.

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