Department of Medicine, Division of Cardiology, Mandel Center for Heart and Vascular Research, and the Duke Cardiovascular Research Center, Duke University Medical Center, Durham, North California, USA.
Houston Methodist Research Institute, Department of Cardiovascular Sciences, Houston, Texas, USA.
Stem Cells. 2018 Aug;36(8):1198-1209. doi: 10.1002/stem.2833. Epub 2018 Apr 22.
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.
成熟的前体细胞向心肌细胞分化的过程还不甚清楚。我们发现 TLR3 抑制可阻断心肌细胞的成熟；向心肌细胞谱系分化的前体细胞不再表达成熟基因，肌节也不能发育。通过各种方法，我们发现 TLR3 对心肌细胞成熟的作用依赖于核因子 κB（NFκB）的 RelA 亚单位。重要的是，在促进成熟心肌细胞发育的条件下，NFκB 在心肌细胞成熟基因的启动子处明显富集。此外，TLR3-NFκB 通路的激活可增强心肌细胞的成熟。因此，本研究表明 TLR3-NFκB 通路对于前体细胞向成熟心肌细胞的成熟是必需的。《干细胞》2018 年；36:1198-1209。
