Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair

Bernhard Kühn, Federica Del Monte, Roger J. Hajjar, Yuh Shin Chang, Djamel Lebeche, Shima Arab, Mark T. Keating

Research output: Contribution to journalArticlepeer-review

562 Scopus citations

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.

Original languageEnglish
Pages (from-to)962-969
Number of pages8
JournalNature Medicine
Volume13
Issue number8
DOIs
StatePublished - Aug 2007

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