Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair

B Kühn, F Del Monte, RJ Hajjar, YS Chang… - Nature medicine, 2007 - nature.com
B Kühn, F Del Monte, RJ Hajjar, YS Chang, D Lebeche, S Arab, MT Keating
Nature medicine, 2007nature.com
Adult mammalian hearts respond to injury with scar formation and not with cardiomyocyte
proliferation, the cellular basis of regeneration. Although cardiogenic progenitor cells may
maintain myocardial turnover, they do not give rise to a robust regenerative response. Here
we show that extracellular periostin induced reentry of differentiated mammalian
cardiomyocytes into the cell cycle. Periostin stimulated mononucleated cardiomyocytes to go
through the full mitotic cell cycle. Periostin activated αV, β1, β3 and β5 integrins located in …
Abstract
Adult mammalian hearts respond to injury with scar formation and not with cardiomyocyte proliferation, the cellular basis of regeneration. Although cardiogenic progenitor cells may maintain myocardial turnover, they do not give rise to a robust regenerative response. Here we show that extracellular periostin induced reentry of differentiated mammalian cardiomyocytes into the cell cycle. Periostin stimulated mononucleated cardiomyocytes to go through the full mitotic cell cycle. Periostin activated αV, β1, β3 and β5 integrins located in the cardiomyocyte cell membrane. Activation of phosphatidylinositol-3-OH kinase was required for periostin-induced reentry of cardiomyocytes into the cell cycle and was sufficient for cell-cycle reentry in the absence of periostin. After myocardial infarction, periostin-induced cardiomyocyte cell-cycle reentry and mitosis were associated with improved ventricular remodeling and myocardial function, reduced fibrosis and infarct size, and increased angiogenesis. Thus, periostin and the pathway that it regulates may provide a target for innovative strategies to treat heart failure.
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