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.
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In this study, we hypothesized that one of the beneficial effects of mesenchymal stem cell (MSC) microvesicle (MV) administration in lung injury was the restoration of lung protein permeability. Using a transwell coculture system with human lung microvascular endothelial cells (HLMVEC), we demonstrated that MSC MV restored protein permeability to FITC‐dextran (70 kDa) across HLMVECs injured by cytomix in part due to an increase in Ang1 mRNA and protein secretion in the injured endothelium, which prevented “actin stress fiber” formation. Ang1 siRNA pretreatment of MSC MV prior to administration to injured HLMVECs eliminated the therapeutic effect of MV. MSC MV administration restored protein permeability across HLMVEC in part by increasing Ang1 secretion.
Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B
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