ELTD1 as a biomarker for multiple sclerosis: Pre-clinical molecular-targeted studies in a mouse experimental autoimmune encephalomyelitis model.
ELTD1 as a biomarker for multiple sclerosis: Pre-clinical molecular-targeted studies in a mouse experimental autoimmune encephalomyelitis model.
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DOI：
10.1016/j.msard.2021.102786
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发表时间：
2021-04
影响因子：
4
通讯作者：
Axtell RC
中科院分区：
文献类型：
--
作者：
Towner RA;Smith N;Zalles M;Morris S;Toliver M;Saunders D;Lerner M;Kumar G;Axtell RC
多发性硬化（MS）和胶质母细胞瘤（GBM）是影响中枢神经系统（CNS）的两种不同疾病。然而，CNS血管系统的扰动是这两种疾病的标志。ELTD 1（表皮生长因子，latrophilin，和7个跨膜结构域包含蛋白1的染色体1）与血管的发展，并已与肿瘤血管生成。在胶质母细胞瘤中，我们检测到ELTD 1的过度表达，并发现靶向ELTD 1的抗体可以增加动物存活率并减少异种移植GBM模型中的肿瘤体积。GBM模型中临床前数据的RNA-seq分析确定，受抗ELTD 1抗体治疗影响的一些分子途径也被发现与MS相关。在这项研究中，我们使用分子靶向（mt）MR成像和免疫组织化学来评估实验性自身免疫性脑脊髓炎（EAE）（MS的小鼠模型）中的ELTD 1水平。我们发现ELTD 1在患有EAE的小鼠的脑中容易检测到，并且主要存在于胼胝体中。此外，我们发现，使用对比增强MRI（CE-MRI），EAE小鼠大脑中的血脑屏障（BBB）受损，以及使用灌注成像，这些小鼠的大脑和颈脊髓中的相对脑血流量（rCBF）发生变化。这些发现表明，ELTD 1可能是MS中CNS炎症的有希望的生物标志物。
Multiple sclerosis (MS) and glioblastoma (GBM) are two distinct diseases that affect the central nervous system (CNS). However, perturbation in CNS vasculature are hallmarks of both diseases. ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain containing protein 1 on chromosome 1) is associated with vascular development, and has been linked with tumor angiogenesis. In glioblastomas, we detected over-expression of ELTD1, and found that an antibody targeting ELTD1 could increase animal survival and decrease tumor volumes in a xenograft GBM model. RNA-seq analysis of the preclinical data in the model for GBM identified that some of the molecular pathways affected by the anti-ELTD1 antibody therapy are also found to be associated with MS. In this study, we used molecular-targeted (mt) MR imaging and immunohistochemistry to assess ELTD1 levels in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Specifically, we found that ELTD1 is readily detected in the brains of mice with EAE and is predominantly found in the corpus callosum. In addition, we found that the blood-brain barrier (BBB) was compromised in the brains of EAE mice using contrast-enhanced MRI (CE-MRI), as well as altered relative cerebral blood flow (rCBF) in the brains and cervical spinal cords of these mice using perfusion imaging, compared to controls. These findings indicate that ELTD1 may be a promising biomarker for CNS-inflammation in MS.
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影响因子：
1.2
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