Department of Biochemistry, Boston University, Boston, MA, 02118, USA.
Molecular and Translational Medicine Program, Boston University, Boston, MA, 02118, USA.
Anal Bioanal Chem. 2022 Apr;414(9):3005-3015. doi: 10.1007/s00216-022-03929-4. Epub 2022 Feb 2.
Extracellular matrix (ECM) proteins, collectively known as the matrisome, include collagens, glycoproteins, and proteoglycans. Alterations in the matrisome have been implicated in the neurodegenerative pathologies including Parkinson's disease (PD). In this work, we utilized our previously published PD and control proteomics data from human prefrontal cortex and focused our analysis on the matrisome. Among matrisome proteins, we observed a significant enrichment in the expression of type I collagen in PD vs. control samples. We then performed histological analysis on the same samples used for proteomics study, and examined collagen expression using picrosirius red staining. Interestingly, we observed similar trends in collagen abundance in PD vs. control as in our matrisome analysis; thus, this and other histological analyses will be useful as a complementary technique in the future to study the matrisome in PD with a larger cohort, and it may aid in choosing regions of interest for proteomic analysis. Additionally, collagen hydroxyprolination was less variable in PD compared to controls. Glycoproteomic changes in matrisome molecules were also observed in PD relative to aged individuals, especially related to type VI collagen and versican. We further examined the list of differentially expressed matrisome molecules using network topology-based analysis and found that angiogenesis indicated by alterations in decorin and several members of the collagen family was affected in PD. These findings collectively identified matrisome changes associated with PD; further studies with a larger cohort are required to validate the current results.
细胞外基质 (ECM) 蛋白，统称为基质组，包括胶原、糖蛋白和蛋白聚糖。基质组的改变与包括帕金森病 (PD) 在内的神经退行性病变有关。在这项工作中，我们利用之前发表的来自人前额叶皮层的 PD 和对照蛋白质组学数据，重点分析了基质组。在基质组蛋白中，我们观察到 PD 与对照样本相比，I 型胶原的表达显著富集。然后，我们对用于蛋白质组学研究的相同样本进行了组织学分析，并使用苦味酸天狼星红染色检查胶原蛋白的表达。有趣的是，我们观察到 PD 与对照之间的胶原蛋白丰度存在类似的趋势，与我们的基质组分析一致；因此，这种和其他组织学分析将作为未来研究 PD 基质组的一种补充技术非常有用，并且可以帮助选择蛋白质组学分析的感兴趣区域。此外，与对照组相比，PD 中的胶原蛋白羟脯氨酸含量变化较小。与年龄较大的个体相比，PD 中也观察到基质组分子的糖蛋白组变化，尤其是与 VI 型胶原和 versican 相关。我们进一步使用基于网络拓扑的分析方法检查了差异表达的基质组分子列表，发现 PD 中改变的 decorin 和胶原家族的几个成员提示血管生成受到影响。这些发现共同确定了与 PD 相关的基质组变化；需要更大的队列进行进一步研究来验证目前的结果。
