Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B. (22nd April 2018)

• Record Type: Journal Article
• Authors: Hodgkinson, Conrad P.; Pratt, Richard E.; Kirste, Imke; Dal-Pra, Sophie; Cooke, John P.; Dzau, Victor J.
• Is Part Of: Stem cells. Volume 36:Number 8(2018)
• Page Start: 1198
• Page End: 1209
• Publication Date: 2018-04-22
• Subjects: Cardiomyocyte maturation -- Cardiomyocyte development -- Cardiac reprogramming -- Innate immunity -- TLR3 -- MicroRNAs -- Nuclear factor kappa B; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2833
• Languages: English
• ISSNs: 1066-5099

Abstract

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. Abstract : Activation of TLR3 enhances direct cardiac reprogramming.