Multiple sclerosis: Re-expression of a developmental gene in chronic lesions correlates with remyelination
Multiple sclerosis: Re-expression of a developmental gene in chronic lesions correlates with remyelination
复制标题
DOI：
10.1002/ana.410410616
复制
发表时间：
1997-06-01
影响因子：
11.2
通讯作者：
Raine, CS
中科院分区：
文献类型：
--
作者：
Capello, E;Voskuhl, RR;Raine, CS
通过免疫细胞化学和原位杂交技术，分别研究了多发性硬化和非多发性硬化受试者中枢神经系统组织中髓鞘碱性蛋白基因产物外显子2在蛋白质和信息水平的表达。外显子2编码的蛋白质序列通常在发育（髓鞘形成）期间在21 . 5-和20 . 2-kd亚型的髓鞘碱性蛋白，并下调在成人中枢神经系统，其中18。5-和17 . 2-kd亚型占优势，后者由于选择性剪接而缺乏外显子2。外显子2髓鞘碱性蛋白基因产物在多发性硬化样品中很容易证明，最高水平与慢性病变中的髓鞘再生相关，而正常成人中枢神经系统和非多发性硬化材料显示非常低的水平，胎儿人中枢神经系统组织（阳性对照）显示高水平。Wk的结论是，髓鞘修复过程中个体发生事件的重演导致多发性硬化症期间成人中枢神经系统中外显子2编码的蛋白质序列表达增加，这一事件可能是先前观察到的复发期间T细胞激活该蛋白质序列的基础。
Central nervous system tissue from multiple sclerosis and non-multiple sclerosis subjects was studied for the expression of exon 2 myelin basic protein gene products at the protein and message levels by immunocytochemistry and in situ hybridization, respectively. The exon 2-encoded protein sequence is normally expressed during development (myelination) within the 21 . 5- and 20 . 2-kd isoforms of myelin basic protein and is downregulated in the adult central nervous system where the 18 . 5- and 17 . 2-kd isoforms predominate, the latter devoid of exon 2 owing to alternative splicing. Exon 2 myelin basic protein gene products were readily demonstrable in multiple sclerosis samples, the highest levels correlating with remyelination in chronic lesions while normal adult central nervous system and non-multiple sclerosis material showed very low levels and fetal human central nervous system tissue (a positive control) showed high levels. Wk conclude that recapitulation of ontogenetic events during myelin repair accounts for the increased expression of the exon 2-encoded protein sequence in the adult central nervous system during multiple sclerosis, an event that might underly the previously observed T-cell activation to this protein sequence during relapses.