Stephenson Erin Laurel, Jain Rajiv William, Ghorbani Samira, Gorter Rianne Petra, D'Mello Charlotte, Yong Voon Wee
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N 2T9, Canada.
Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2024 Jan 19;25(2):1240. doi: 10.3390/ijms25021240.
The extracellular matrix (ECM) of the central nervous system (CNS) is an interconnected network of proteins and sugars with critical roles in both homeostasis and disease. In neurological diseases, excessive ECM deposition and remodeling impact both injury and repair. CNS lesions of multiple sclerosis (MS), a chronic inflammatory and degenerative disease, cause prominent alterations of the ECM. However, there are a lack of data investigating how the multitude of ECM members change in relation to each other and how this affects the MS disease course. Here, we evaluated ECM changes in MS lesions compared to a control brain using databases generated in-house through spatial mRNA-sequencing and through a public resource of single-nucleus RNA sequencing previously published by Absinta and colleagues. These results underline the importance of publicly available datasets to find new targets of interest, such as the ECM. Both spatial and public datasets demonstrated widespread changes in ECM molecules and their interacting proteins, including alterations to proteoglycans and glycoproteins within MS lesions. Some of the altered ECM members have been described in MS, but other highly upregulated members, including the SPARC family of proteins, have not previously been highlighted. SPARC family members are upregulated in other conditions by reactive astrocytes and may influence immune cell activation and MS disease course. The profound changes to the ECM in MS lesions deserve more scrutiny as they impact neuroinflammation, injury, and repair.
中枢神经系统（CNS）的细胞外基质（ECM）是一个由蛋白质和糖类构成的相互连接的网络，在稳态和疾病中都起着关键作用。在神经疾病中，ECM的过度沉积和重塑会影响损伤和修复。多发性硬化症（MS）是一种慢性炎症性和退行性疾病，其CNS病变会导致ECM发生显著改变。然而，目前缺乏关于众多ECM成员如何相互变化以及这如何影响MS病程的数据。在这里，我们使用通过空间mRNA测序内部生成的数据库以及先前由阿宾塔及其同事发表的单核RNA测序公共资源，评估了与对照脑相比MS病变中的ECM变化。这些结果强调了公开可用数据集对于寻找新的感兴趣靶点（如ECM）的重要性。空间数据集和公共数据集均显示ECM分子及其相互作用蛋白发生了广泛变化，包括MS病变中蛋白聚糖和糖蛋白的改变。一些改变的ECM成员在MS中已有描述，但其他高度上调的成员，包括SPARC蛋白家族，此前尚未被重点提及。SPARC家族成员在其他情况下会被反应性星形胶质细胞上调，并可能影响免疫细胞激活和MS病程。MS病变中ECM的深刻变化值得更多审视，因为它们会影响神经炎症、损伤和修复。
