Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair

Ildiko Bock-Marquette, Ankur Saxena, Michael D. White, J. Michael DiMaio, Deepak Srivastava

Research output: Contribution to journalArticle

524 Scopus citations

Abstract

Heart disease is a leading cause of death in newborn children and in adults. Efforts to promote cardiac repair through the use of stem cells hold promise but typically involve isolation and introduction of progenitor cells. Here, we show that the G-actin sequestering peptide thymosin β4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin β4. We found that thymosin β4 formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt (also known as protein kinase B). After coronary artery ligation in mice, thymosin β4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival and improved cardiac function. These findings suggest that thymosin β4 promotes cardiomyocyte migration, survival and repair and the pathway it regulates may be a new therapeutic target in the setting of acute myocardial damage.

Original languageEnglish (US)
Pages (from-to)466-472
Number of pages7
JournalNature
Volume432
Issue number7016
DOIs
StatePublished - Nov 25 2004

ASJC Scopus subject areas

  • General

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    Bock-Marquette, I., Saxena, A., White, M. D., DiMaio, J. M., & Srivastava, D. (2004). Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, 432(7016), 466-472. https://doi.org/10.1038/nature03000