Department of Biology, Maynooth University, National University of Ireland, Maynooth W23F2H6, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth W23F2H6, Co. Kildare, Ireland.
Institute of Physiology II, University of Bonn, D53115 Bonn, Germany.
Eur J Cell Biol. 2020 Jan;99(1):151059. doi: 10.1016/j.ejcb.2019.151059. Epub 2019 Nov 18.
The X-linked inherited muscle wasting disease Duchenne muscular dystrophy, which is caused by primary abnormalities in the membrane cytoskeletal protein dystrophin, is a multi-system disorder. Highly progressive forms of dystrophinopathy are associated with a complex secondary pathophysiology, including renal dysfunction. It was therefore of interest to carry out a systematic survey of potential proteome-wide changes in the kidney of the established mdx-4cv mouse model of dystrophinopathy. Of 5878 mass spectrometrically identified kidney proteins, 82 versus 142 proteins were shown to be decreased or increased, respectively, in association with muscular dystrophy. The most decreased versus increased protein species are the ACSM3 isoform of mitochondrial acyl-coenzyme A synthetase and the FABP1 isoform of fatty acid binding protein, respectively. Both proteomic findings were verified by immunofluorescence microscopy and immunoblot analysis. Interestingly, haematoxylin/eosin staining indicated diffuse whitish deposits in the mdx-4cv kidney, and an increased intensity of Sudan Black labelling of kidney cells revealed ectopic fat deposition. Although the proteomic results and cell biological findings do not demonstrate a direct functional link between increased FABP1 and fat accumulation, the results suggest that the up-regulation of FABP1 may be related to abnormal fat metabolism. This makes FABP1 potentially a novel pathobiochemical indicator for studying kidney abnormalities in the mdx-4cv model of dystrophinopathy.
X 连锁遗传性肌肉萎缩疾病杜氏肌营养不良症是由膜细胞骨架蛋白肌营养不良蛋白的主要异常引起的，是一种多系统疾病。高度进行性形式的肌营养不良症与复杂的继发性病理生理学有关，包括肾功能障碍。因此，对已建立的肌营养不良症 mdx-4cv 小鼠模型的肾脏中的潜在蛋白质组进行系统调查很有意义。在鉴定出的 5878 种肾脏蛋白质中，分别有 82 种和 142 种蛋白质与肌肉萎缩相关而减少或增加。减少最多的与增加最多的蛋白质分别是线粒体酰基辅酶 A 合成酶的 ACSM3 同工型和脂肪酸结合蛋白的 FABP1 同工型。这两种蛋白质组学发现都通过免疫荧光显微镜和免疫印迹分析得到了验证。有趣的是，苏木精/伊红染色表明 mdx-4cv 肾脏中有弥漫性白色沉积物，苏丹黑染色肾脏细胞的强度增加表明异位脂肪沉积。尽管蛋白质组学结果和细胞生物学发现并没有证明 FABP1 增加与脂肪积累之间存在直接的功能联系，但结果表明 FABP1 的上调可能与异常脂肪代谢有关。这使得 FABP1 成为研究肌营养不良症 mdx-4cv 模型中肾脏异常的潜在新的病理生物化学指标。
