BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions
BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions
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DOI：
10.1016/j.bbi.2011.05.003
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发表时间：
2011-11-01
影响因子：
15.1
通讯作者：
Beyer, C.
中科院分区：
文献类型：
--
作者：
Kipp, M.;Gingele, S.;Beyer, C.
一些证据表明，重新髓鞘形成是实现轴突保护的最有效机制之一。由于尚不清楚的原因，在多发性硬化症(MS)中，这一过程通常是不完整的或失败的。激活的星形胶质细胞似乎能够促进或抑制内源性修复过程。需要更好地了解多发性硬化症的再髓鞘形成及其失败的可能原因。使用公认的毒性脱髓鞘铜带模型，我们创建了内源性再髓鞘形成能力强健或受损的病变。用Affymetrix基因芯片(R)阵列分析病变组织的mRNA表达水平。一个发现是免疫和应激反应因子在这组基因中占主导地位，这些基因被归类为支持重新髓鞘形成的因子。我们进一步证明，再生髓鞘能力受损的病变显示放射状胶质细胞标志脑脂结合蛋白(BLBP，也称为B-FABP或FABP7)的表达较弱。BLBP在激活的星形胶质细胞中的表达与少突胶质前体细胞的存在相关。在实验性自身免疫性脑脊髓炎缓解期也可检测到表达BLBP的星形胶质细胞。此外，表达BLBP的星形胶质细胞在早期MS的皮损中最多，而在病程较长的(慢性)活动皮损边缘的星形胶质细胞明显较少。转染实验表明，BLBP对U87星形细胞瘤细胞生长因子的表达有调节作用。总之，我们提供的证据表明，BLBP在激活的星形胶质细胞中的表达与病程呈负相关，并与重新髓鞘形成失败平行。(C)2011 Elsevier Inc.保留所有权利。
Several lines of evidence indicate that remyelination represents one of the most effective mechanisms to achieve axonal protection. For reasons that are not yet understood, this process is often incomplete or fails in multiple sclerosis (MS). Activated astrocytes appear to be able to boost or inhibit endogenous repair processes. A better understanding of remyelination in MS and possible reasons for its failure is needed.Using the well-established toxic demyelination cuprizone model, we created lesions with either robust or impaired endogenous remyelination capacity. Lesions were analyzed for mRNA expression levels by Affymetrix GeneChip (R) arrays. One finding was the predominance of immune and stress response factors in the group of genes which were classified as remyelination-supporting factors. We further demonstrate that lesions with impaired remyelination capacity show weak expression of the radial-glia cell marker brain lipid binding protein (BLBP, also called B-FABP or FABP7). The expression of BLBP in activated astrocytes correlates with the presence of oligodendrocyte progenitor cells. BLBP-expressing astrocytes are also detected in experimental autoimmune encephalomyelitis during the remission phase. Furthermore, highest numbers of BLBP-expressing astrocytes were evident in lesions of early MS, whereas significantly less are present at the rim of (chronic)-active lesions from patients with long disease duration. Transfection experiments show that BLBP regulates growth factor expression in U87 astrocytoma cells. In conclusion, we provide evidence that expression of BLBP in activated astrocytes negatively correlates with disease duration and in parallel with remyelination failure. (C) 2011 Elsevier Inc. All rights reserved.