Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis
Bone morphogenetic proteins 4, 6, and 7 are up-regulated in mouse spinal cord during experimental autoimmune encephalomyelitis
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DOI：
10.1002/jnr.21462
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Grinspan, Judith B.
中科院分区：
文献类型：
--
作者：
Ara, Jahan;See, Jill;Grinspan, Judith B.
尽管多发性硬化症（MS）中发生自发性髓鞘再生，但髓鞘修复的程度通常不足以恢复正常功能。残留在非髓鞘再生MS斑块中的少突胶质细胞前体可能受到抑制信号的限制。骨形态发生蛋白（BMP）被认为是少突胶质细胞发育的抑制因子和星形胶质细胞生成的诱导因子。我们假设BMP在MS病变中上调，并在脱髓鞘和星形胶质细胞增生中发挥作用。我们检测了C57 BL/ 6小鼠中髓鞘少突胶质细胞糖蛋白（MOG）肽诱导的MS（慢性实验性自身免疫性脑脊髓炎）动物模型中BMP的表达。免疫后14天，与对照小鼠相比，MOG-肽EAE小鼠的腰脊髓表现出突出的星形胶质细胞增生、炎性细胞浸润和髓磷脂蛋白表达中断。定量RT-PCR显示，BMP 4，BMP 6，和BMP 7 mRNA的表达增加2- 4倍，在腰脊髓的动物与症状性EAE相比，在溶剂处理和未处理的对照组在第14，21和42天免疫。BMP 2 mRNA表达无明显变化。BMP 4 mRNA在所有动物的脊髓中比编码BMP 2、BMP 6和BMP 7的mRNA丰富得多。免疫印迹分析证实了EAE动物中BMP 4的表达增加。免疫组织化学显示MOG肽EAE动物炎症区域的BMP 4免疫反应性增加。BMP 4标记主要限于巨噬细胞，但有时与星形胶质细胞和少突胶质细胞相关。这些结果表明，BMP家族的成员在成人脊髓中差异表达，并在EAE期间上调。(c)2007 Wiley-Liss，Inc.
Although spontaneous remyelination occurs in multiple sclerosis (MS), the extent of myelin repair is often inadequate to restore normal function. Oligodendrocyte precursors remaining in nonremyelinating MS plaques may be restricted by an inhibitory signal. Bone morphogenetic proteins (BMPs) have been implicated as repressors of oligodendrocyte development and inducers of astrogliogenesis. We hypothesized that BMPs are up-regulated in MS lesions and play a role in demyelination and astrogliosis. We examined expression of BMPs in an animal model of MS, chronic experimental autoimmune encephalomyelitis (EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/ 6 mice. By 14 days postimmunization, compared to those of control mice, the lumbar spinal cords of MOG-peptide EAE mice demonstrated prominent astrogliosis, infiltration of inflammatory cells, and disrupted expression of myelin proteins. Quantitative RT-PCR showed that expression of BMP4, BMP6, and BMP7 mRNA increased 2- to 4-fold in the lumbar spinal cords of animals with symptomatic EAE versus in vehicle-treated and untreated controls on days 14, 21, and 42 postimmunization. BMP2 mRNA expression was not altered. BMP4 mRNA was much more abundant in the spinal cords of all animals than was mRNA encoding BMP2, BMP6, and BMP7. Immunoblot analysis confirmed the increased expression of BMP4 in the EAE animals. Immunohistochemistry revealed increased BMP4 immunoreactivity in areas of inflammation in MOG-peptide EAE animals. BMP4 labeling was mostly limited to macrophages but was sometimes associated with astrocytes and oligodendrocytes. These results indicate that members of the BMP family are differentially expressed in adult spinal cord and are up-regulated during EAE. (c) 2007 Wiley-Liss, Inc.