Article abstract
Nature Medicine 13, 962 - 969 (2007)
Published online: 15 July 2007 | doi:10.1038/nm1619
Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair
Bernhard Kühn1, Federica del Monte2, Roger J Hajjar2,4, Yuh-Shin Chang3, Djamel Lebeche2,4, Shima Arab1 & Mark T Keating1,4
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 
V, 
1, 3 and 5 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.
- Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
- Cardiovascular Research Center, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA.
- Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA).
- Present addresses: Cardiovascular Research Center, Mount Sinai School of Medicine, One Gustave Levy Place, New York, New York 10029, USA (R.J.H., D.L.); Novartis Institutes for BioMedical Research, Inc., 500 Technology Square, Cambridge, Massachusetts 02139, USA (M.T.K.).
Correspondence to: Bernhard Kühn1 e-mail: bernhard.kuhn@cardio.chboston.org
Correspondence to: Mark T Keating1,4 e-mail: mark.keating@novartis.com
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