Open AccessCardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B
Author(s) -
Hodgkinson Conrad P.,
Pratt Richard E.,
Kirste Imke,
DalPra Sophie,
Cooke John P.,
Dzau Victor J.
Publication year - 2018
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2833
Subject(s) - biology , microbiology and biotechnology , tlr3 , nfkb1 , sarcomere , transcription factor , myocyte , gene , genetics , receptor , toll like receptor , innate immune system
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. S tem C ells 2018;36:1198–1209