Human Dystrophin Dp71ab Enhances the Proliferation of Myoblasts Across Species But Not Human Nonmyoblast Cells.

Dystrophin Dp71 is an isoform produced from the Dp71 promoter in intron 62 of the DMD gene, mutations in which cause Duchenne muscular dystrophy. Dp71 is involved in various cellular processes and comprises more than 10 isoforms produced by alternative splicing. Dp71ab, in which both exons 71 and 78 are deleted, has a hydrophobic C-terminus that is hydrophilic in Dp71. Therefore, Dp71ab is believed to have different roles from Dp71. Previously, we reported that Dp71ab enhanced the proliferation of human myoblasts. Here, we further characterized Dp71ab, focusing on the activation of cell proliferation. Dp71ab increased the proliferation of immortalized human myoblasts in a dose-dependent manner. In contrast, Dp71 suppressed proliferation in a dose-dependent manner. Consistent with these opposite effects, eGFP-tagged Dp71ab and mCherry-tagged Dp71 showed different cellular distributions, with Dp71ab mostly in the nucleus. Notably, human Dp71ab enhanced the proliferation of rat and mouse myoblasts. Despite these findings, human Dp71ab did not enhance the proliferation of human nonmyoblast cells, including rhabdomyosarcoma cells. We concluded that Dp71ab is a myoblast-specific proliferation enhancer. In further studies, Dp71ab will be employed for the expansion of myoblasts in clinical settings.

抗肌萎缩蛋白Dp71是由DMD基因内含子62中的Dp71启动子产生的一种异构体，该基因的突变会导致杜氏肌营养不良症。Dp71参与多种细胞过程，并且包含10多种通过可变剪接产生的异构体。在Dp71ab中，外显子71和78均缺失，其具有一个疏水的C末端，而在Dp71中该末端是亲水的。因此，人们认为Dp71ab与Dp71具有不同的作用。此前，我们报道了Dp71ab可促进人成肌细胞的增殖。在此，我们进一步对Dp71ab进行了表征，重点关注其对细胞增殖的激活作用。Dp71ab以剂量依赖的方式增加永生化人成肌细胞的增殖。相反，Dp71以剂量依赖的方式抑制增殖。与这些相反的作用一致，带有eGFP标签的Dp71ab和带有mCherry标签的Dp71显示出不同的细胞分布，Dp71ab主要在细胞核中。值得注意的是，人Dp71ab可促进大鼠和小鼠成肌细胞的增殖。尽管有这些发现，但人Dp71ab并不能促进人非成肌细胞（包括横纹肌肉瘤细胞）的增殖。我们得出结论，Dp71ab是一种成肌细胞特异性的增殖促进剂。在进一步的研究中，Dp71ab将被用于临床环境中以扩增成肌细胞。