Filling the Gaps - A Call for Comprehensive Analysis of Extracellular Matrix of the Glial Scar in Region- and Injury-Specific Contexts
Filling the Gaps - A Call for Comprehensive Analysis of Extracellular Matrix of the Glial Scar in Region- and Injury-Specific Contexts
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DOI：
10.3389/fncel.2020.00032
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发表时间：
2020-02-20
影响因子：
5.3
通讯作者：
Goetz, Magdalena
中科院分区：
文献类型：
--
作者：
Kjell, Jacob;Goetz, Magdalena
中枢神经系统(CNS)损伤会导致慢性瘢痕形成，干扰功能并抑制修复。细胞外基质(ECM)在瘢痕组织中占有重要地位，对细胞行为起着重要的调节作用。然而，关于细胞外基质蛋白质组的全面信息在很大程度上是缺乏的，而且通常没有考虑到区域和损伤特定的差异。这些方面是我们对损伤和疤痕形成的看法的重点。为了强调这种综合蛋白质组分析的重要性，我们包括了用新的分析工具获得的瘢痕中ECM成分的数据，并展示了单核细胞对创伤性脑损伤(TBI)后ECM成分的贡献。使用CCR2-/-小鼠系减少单核细胞侵袭，逐步去细胞和蛋白质组学可以确定单核细胞依赖的细胞外基质成分和胶质瘢痕的结构。我们发现，在没有单核细胞侵袭的情况下，细胞外基质蛋白Tgm1、Itih(1、2和3)和FTL显著减少。我们还描述了包含具有独特组成的区域的SCAR ECM，并且与TBI后早期获得的蛋白质组相比较，显示出亚急性签名。这些结果是根据损伤、区域和时间特定的瘢痕形成调节来讨论的，强调迫切需要使用全面的ECM分析来区分损伤条件和中枢神经系统区域。
Central nervous system (CNS) injury results in chronic scar formation that interferes with function and inhibits repair. Extracellular matrix (ECM) is prominent in the scar and potently regulates cell behavior. However, comprehensive information about the ECM proteome is largely lacking, and region- as well as injury-specific differences are often not taken into account. These aspects are the focus of our perspective on injury and scar formation. To highlight the importance of such comprehensive proteome analysis we include data obtained with novel analysis tools of the ECM composition in the scar and show the contribution of monocytes to the ECM composition after traumatic brain injury (TBI). Monocyte invasion was reduced using the CCR2-/- mouse line and step-wise de-cellularization and proteomics allowed determining monocyte-dependent ECM composition and architecture of the glial scar. We find significant reduction in the ECM proteins Tgm1, Itih (1,2, and 3), and Ftl in the absence of monocyte invasion. We also describe the scar ECM comprising zones with distinctive composition and show a subacute signature upon comparison to proteome obtained at earlier times after TBI. These results are discussed in light of injury-, region- and time-specific regulation of scar formation highlighting the urgent need to differentiate injury conditions and CNS-regions using comprehensive ECM analysis.