Matrisome changes in Parkinson's disease.
Matrisome changes in Parkinson's disease.
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DOI：
10.1007/s00216-022-03929-4
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发表时间：
2022-04
影响因子：
4.3
通讯作者：
Zaia J
中科院分区：
文献类型：
--
作者：
Downs M;Sethi MK;Raghunathan R;Layne MD;Zaia J
细胞外基质（ECM）蛋白，统称为基质体，包括胶原蛋白、糖蛋白和蛋白聚糖。基质体的改变与神经退行性疾病包括帕金森病（PD）有关。在这项工作中，我们利用我们之前发表的PD和来自人类前额叶皮层的对照蛋白质组学数据，并将我们的分析集中在基质上。在基质蛋白中，我们观察到PD中I型胶原蛋白的表达与对照样品相比显著富集。然后，我们对用于蛋白质组学研究的相同样品进行组织学分析，并使用小天狼星红染色检测胶原蛋白表达。有趣的是，我们观察到PD组与对照组的胶原丰度趋势与我们的基质分析相似；因此，该方法和其他组织学分析方法将在未来更大的队列中作为一种补充技术来研究帕金森病的基质体，它可能有助于选择感兴趣的区域进行蛋白质组学分析。此外，与对照组相比，PD患者的胶原羟基脯氨酸变化较小。PD中基质体分子的糖蛋白组学变化也与老年个体相关，特别是与VI型胶原和花蜜聚糖相关。我们进一步使用基于网络拓扑的分析检查了差异表达的基质分子列表，发现血管生成受decorin和胶原家族成员改变的影响。这些发现共同确定了与PD相关的基质改变；需要更多的研究来验证目前的结果。
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.
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作者：
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