Department of Neonatology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
Life Sci. 2019 Dec 15;239:117040. doi: 10.1016/j.lfs.2019.117040. Epub 2019 Nov 6.
Congenital heart disease (CHD) is the most common birth defect in newborns. There is increasing evidence that apoptosis and remodeling of the cardiomyoblasts are the major pathology of CHD. Previous research found that T-box transcription factor 3 (TBX3) was compulsory for the regulation of proliferation, cell cycle arrest and apoptosis in various cells. Hence, TBX3 might be involved in the treatment of CHD. The primary aim of this study was to study the effects of TBX3 on apoptosis in aged cardiomyoblasts and investigate the latent mechanism. In the present study, we found TBX3 knockdown induced proliferation inhibition, cell cycle arrest and apoptosis accompanied by mitochondrial dysfunction in cardiomyoblasts at passage 10 to 15. Apoptosis-inducing effects of TBX3 silence could be neutralized by silencing P21 using specific siRNA. In addition, the mRNA and protein expression levels of TBX3 in the heart tissues of sporadic type CHD donors were obviously down-regulated. In conclusion, we demonstrated that TBX3 deficiency accelerated apoptosis via directly regulating P21 expression in senescent cardiomyoblasts.
先天性心脏病（CHD）是新生儿中最常见的出生缺陷。越来越多的证据表明，心肌细胞的凋亡和重塑是 CHD 的主要病理学改变。先前的研究发现，T 盒转录因子 3（TBX3）是调节各种细胞增殖、细胞周期阻滞和凋亡的必需因子。因此，TBX3 可能参与 CHD 的治疗。本研究的主要目的是研究 TBX3 对衰老心肌细胞凋亡的影响，并探讨潜在的机制。在本研究中，我们发现 TBX3 敲低可诱导传代 10-15 代的心肌细胞增殖抑制、细胞周期阻滞和凋亡，并伴有线粒体功能障碍。使用特异性 siRNA 沉默 P21 可中和 TBX3 沉默的促凋亡作用。此外，散发性 CHD 供体心脏组织中 TBX3 的 mRNA 和蛋白表达水平明显下调。综上所述，我们证明了 TBX3 缺乏通过直接调节衰老心肌细胞中的 P21 表达来加速细胞凋亡。
