Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B

Research output: Contribution to journalArticle

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

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 1 2018

PMID: 29676038

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Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B. / Hodgkinson, Conrad P.; Pratt, Richard E.; Kirste, Imke; Dal-Pra, Sophie; Cooke, John P.; Dzau, Victor J.

In: Stem Cells, Vol. 36, No. 8, 01.08.2018, p. 1198-1209.

Research output: Contribution to journalArticle

Harvard

Hodgkinson, CP, Pratt, RE, Kirste, I, Dal-Pra, S, Cooke, JP & Dzau, VJ 2018, 'Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B' Stem Cells, vol. 36, no. 8, pp. 1198-1209. https://doi.org/10.1002/stem.2833

APA

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

Vancouver

Hodgkinson CP, Pratt RE, Kirste I, Dal-Pra S, Cooke JP, Dzau VJ. Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B. Stem Cells. 2018 Aug 1;36(8):1198-1209. https://doi.org/10.1002/stem.2833

Author

Hodgkinson, Conrad P. ; Pratt, Richard E. ; Kirste, Imke ; Dal-Pra, Sophie ; Cooke, John P. ; Dzau, Victor J. / Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B. In: Stem Cells. 2018 ; Vol. 36, No. 8. pp. 1198-1209.

BibTeX

@article{865e32ad9dac4dffba82153717c45932,
title = "Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B",
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.",
keywords = "Cardiac reprogramming, Cardiomyocyte development, Cardiomyocyte maturation, Innate immunity, MicroRNAs, Nuclear factor kappa B, TLR3",
author = "Hodgkinson, {Conrad P.} and Pratt, {Richard E.} and Imke Kirste and Sophie Dal-Pra and Cooke, {John P.} and Dzau, {Victor J.}",
year = "2018",
month = "8",
day = "1",
doi = "10.1002/stem.2833",
language = "English (US)",
volume = "36",
pages = "1198--1209",
journal = "Stem Cells",
issn = "1066-5099",
number = "8",

}

RIS

TY - JOUR

T1 - Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B

AU - Hodgkinson, Conrad P.

AU - Pratt, Richard E.

AU - Kirste, Imke

AU - Dal-Pra, Sophie

AU - Cooke, John P.

AU - Dzau, Victor J.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - Cardiac reprogramming

KW - Cardiomyocyte development

KW - Cardiomyocyte maturation

KW - Innate immunity

KW - MicroRNAs

KW - Nuclear factor kappa B

KW - TLR3

UR - http://www.scopus.com/inward/record.url?scp=85051439081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051439081&partnerID=8YFLogxK

U2 - 10.1002/stem.2833

DO - 10.1002/stem.2833

M3 - Article

VL - 36

SP - 1198

EP - 1209

JO - Stem Cells

T2 - Stem Cells

JF - Stem Cells

SN - 1066-5099

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ER -

ID: 40337543