Department of Environmental Toxicology, University of California, Davis, CA.
Division of Biostatistics, Department of Public Health Sciences, Clinical and Translational Science Center Biostatistics Core, University of California, Davis, CA.
J Proteomics. 2017 Aug 8;165:132-137. doi: 10.1016/j.jprot.2017.06.017. Epub 2017 Jun 23.
Callus samples from the ball and the arch of the foot, collected on tape circles, were compared by shotgun proteomic profiling. Pachyonychia congenita subjects were sampled who exhibited a mutation in KRT6A, KRT6B, KRT6C, KRT16 or KRT17, and the proteins were digested and analyzed by tandem mass spectrometry. In comparison with samples from unaffected control subjects, those from subjects with KRT6A or KRT16 mutations displayed the most differences in profile from normal, while those from subjects with KRT6C or KRT17 mutations showed few differences from normal. The profiles from subjects with KRT6B mutations were intermediate in protein profile differences. Degree of departure from the normal profile could be estimated by expression of numerous proteins in callus from the ball of the foot that were consistently different. By contrast, the protein profile from the arch of the foot was hardly affected. The results provide a foundation for noninvasive monitoring of the efficacy of treatments with quantitative assessment of departure from the normal phenotype.
Pachyonychia congenita is an orphan disease in which the connection between the basic defect (keratin mutation) and debilitating symptoms (severe plantar pain) is poorly understood. Present work addresses the degree to which the protein profile is altered in the epidermis where the severe pain originates. The results indicate that the mutated keratins differ greatly in the degree to which they elicit perturbations in protein profile. In those cases with markedly altered protein levels, monitoring the callus profile may provide an objective measure of treatment efficacy.
通过 shotgun 蛋白质组学分析对取自足底球部和弓部的胶布圈采集的胼胝样本进行了比较。对 KRT6A、KRT6B、KRT6C、KRT16 或 KRT17 基因突变的先天性厚甲症患者进行了采样，对蛋白质进行了消化和串联质谱分析。与未受影响的对照受试者的样本相比，KRT6A 或 KRT16 突变受试者的样本与正常样本的差异最大，而 KRT6C 或 KRT17 突变受试者的样本与正常样本的差异最小。KRT6B 突变受试者的样本在蛋白质图谱差异方面处于中间位置。可以通过足底球部胼胝中大量差异表达的蛋白质来估计与正常图谱的偏离程度。相比之下，弓部的蛋白质图谱几乎不受影响。这些结果为非侵入性监测治疗效果提供了基础，并可对与正常表型的偏离程度进行定量评估。
先天性厚甲症是一种孤儿病，其基本缺陷（角蛋白突变）与衰弱症状（严重足底疼痛）之间的联系尚不清楚。目前的工作研究了严重疼痛起源的表皮中蛋白质图谱改变的程度。结果表明，突变角蛋白在引起蛋白质图谱紊乱的程度上有很大差异。在那些蛋白质水平明显改变的情况下，监测胼胝的图谱可能为治疗效果提供客观的衡量标准。
