Adenoviral delivery of human CDC5 promotes G2/M progression and cell division in neonatal ventricular cardiomyocytes.
Adenoviral delivery of human CDC5 promotes G2/M progression and cell division in neonatal ventricular cardiomyocytes.
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人 CDC5 的腺病毒递送促进新生儿心室心肌细胞的 G2/M 进展和细胞分裂。
DOI：
10.1038/sj.gt.3302737
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Bernstein,HS
中科院分区：
文献类型：
--
作者：
Williams,SD;Zhu,H;Zhang,L;Bernstein,HS
心力衰竭是由心肌细胞的累积死亡和剩余细胞无法再生引起的。通过过度表达E1 A或E2 F1对心肌细胞进行转录重编程的努力受到心肌细胞不能进入并完成有丝分裂的限制。人CDC 5（hCDC 5）是前体mRNA剪接复合物的一种组分，已被证明可调节异步分裂细胞中的G2/M转运。我们现在表明，共感染的重组腺病毒表达E1 A/E1 B和hCDC 5促进细胞周期的重新进入和G2/M期进展后，有丝分裂心肌细胞。E1 A/E1 B和hCDC 5的共表达诱导细胞周期蛋白依赖性激酶1和细胞周期蛋白B1的核定位，并且足以促进有丝分裂进入，如仅在共感染细胞中通过有丝分裂指数的增加所确定的。E1 A/E1 B和hCDC 5促进细胞分裂，如通过共感染后心肌细胞数量的增加所证明的。因此，E1 A/E1 B和hCDC 5的过表达导致细胞周期重新进入、DNA合成、细胞分裂和心肌细胞数量增加，表明新心肌细胞的形成。这些研究表明，G1/S期转录调节因子，与前mRNA剪接因子，如CDC 5，调节限速G2/M靶基因组合，可能证明在开发刺激心肌再生的疗法中是有用的。
Heart failure results from the cumulative death of cardiomyocytes, and the inability of remaining cells to regenerate. Efforts toward transcriptional reprogramming of cardiomyocytes by overexpressing E1A or E2F1 have been limited by the inability of cardiomyocytes to enter and complete mitosis. Human CDC5 (hCDC5), a component of the pre-mRNA splicing complex, has been shown to regulate G2/M transit in asynchronously dividing cells. We now show that co-infection of recombinant adenoviruses expressing E1A/E1B and hCDC5 promotes cell cycle re-entry and G2/M progression in post-mitotic cardiomyocytes. Co-expression of E1A/E1B and hCDC5 induced nuclear localization of cyclin-dependent kinase 1 and cyclin B1, and was sufficient to promote mitotic entry as determined by an increase in mitotic index only in co-infected cells. E1A/E1B and hCDC5 promoted cell division, as evidenced by an increase in the number of cardiomyocytes following co-infection. Thus, overexpression of E1A/E1B and hCDC5 resulted in cell cycle re-entry, DNA synthesis, cell division, and an increase in cardiomyocyte number, suggesting the formation of new cardiomyocytes. These studies suggest that G1/S-phase transcriptional regulators, in combination with pre-mRNA splicing factors, such as CDC5, that regulate rate-limiting G2/M target genes may prove useful in developing therapies to stimulate myocardial regeneration.