Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B

Conrad P. Hodgkinson, Richard E. Pratt, Imke Kirste, Sophie Dal-Pra, John P. Cooke, Victor J. Dzau

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The process by which committed precursors mature into cardiomyocytes is poorly understood. We found that TLR3 inhibition blocked cardiomyocyte maturation; precursor cells committed to the cardiomyocyte lineage failed to express maturation genes and sarcomeres did not develop. Using various approaches, we found that the effects of TLR3 upon cardiomyocyte maturation were dependent upon the RelA subunit of nuclear factor kappa B (NFκB). Importantly, under conditions that promote the development of mature cardiomyocytes NFκB became significantly enriched at the promoters of cardiomyocyte maturation genes. Furthermore, activation of the TLR3-NFκB pathway enhanced cardiomyocyte maturation. This study, therefore, demonstrates that the TLR3-NFκB pathway is necessary for the maturation of committed precursors into mature cardiomyocytes. Stem Cells 2018;36:1198–1209.

Original languageEnglish (US)
Pages (from-to)1198-1209
Number of pages12
JournalSTEM CELLS
Volume36
Issue number8
DOIs
StatePublished - Aug 2018

Keywords

  • Cardiac reprogramming
  • Cardiomyocyte development
  • Cardiomyocyte maturation
  • Innate immunity
  • MicroRNAs
  • Nuclear factor kappa B
  • TLR3

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Hodgkinson, C. P., Pratt, R. E., Kirste, I., Dal-Pra, S., Cooke, J. P., & Dzau, V. J. (2018). Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B. STEM CELLS, 36(8), 1198-1209. https://doi.org/10.1002/stem.2833