Dowling Paul, Gargan Stephen, Zweyer Margit, Henry Michael, Meleady Paula, Swandulla Dieter, Ohlendieck Kay
Department of Biology, Maynooth University, National University of Ireland, Maynooth, Co. Kildare W23F2H6, Ireland.
Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare W23F2H6, Ireland.
iScience. 2020 Aug 26;23(9):101500. doi: 10.1016/j.isci.2020.101500. eCollection 2020 Sep 25.
Duchenne muscular dystrophy is primarily characterized by progressive muscle wasting due to deficiency in the membrane cytoskeletal protein dystrophin but is also associated with body-wide cellular disturbances in a variety of non-muscle tissues. In this study, we have focused on the comparative proteomic analysis of the spleen and established considerable changes in this crucial secondary lymphoid organ from the genetic mouse model of dystrophinopathy. An apparent short isoform of dystrophin and associated glycoproteins were identified in spleen by mass spectrometry but appear not be affected in muscular dystrophy. In contrast, the spleen showed significant proteome-wide changes in other protein species that are involved in metabolism, signaling, and cellular architecture. Since the spleen plays a key role in the immune response, these proteomic alterations may reflect pathophysiological cross talk between the lymphoid system and dystrophic muscles, which are affected by both fiber degeneration and inflammation.
杜氏肌营养不良症的主要特征是由于膜细胞骨架蛋白肌营养不良蛋白缺乏导致进行性肌肉萎缩，但也与多种非肌肉组织的全身性细胞紊乱有关。在本研究中，我们专注于脾脏的比较蛋白质组学分析，并在肌营养不良症基因小鼠模型的这个关键二级淋巴器官中发现了相当大的变化。通过质谱法在脾脏中鉴定出一种明显的肌营养不良蛋白短异构体及其相关糖蛋白，但在肌肉营养不良症中似乎未受影响。相比之下，脾脏在参与代谢、信号传导和细胞结构的其他蛋白质种类中显示出显著的蛋白质组范围变化。由于脾脏在免疫反应中起关键作用，这些蛋白质组改变可能反映了淋巴系统和营养不良肌肉之间的病理生理相互作用，而这两者都受到纤维变性和炎症的影响。
