Cord blood administration induces oligodendrocyte survival through alterations in gene expression.

Cord blood administration induces oligodendrocyte survival through alterations in gene expression.
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DOI:
10.1016/j.brainres.2010.09.078
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发表时间:
2010-12-17
期刊:
影响因子:
2.9
通讯作者:
Pennypacker KR
Pennypacker KR
中科院分区:
医学3区
文献类型:
--
作者:
Rowe DD;Leonardo CC;Hall AA;Shahaduzzaman MD;Collier LA;Willing AE;Pennypacker KR

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少突胶质细胞(OLs)是大脑白质中的主要细胞类型,对结构完整性和适当的神经信号传导至关重要。我们对中风引起的OL功能障碍知之甚少。我们的实验室已经证明,输注人脐带血(HUCB)细胞在体内保护纹状体白质束,并直接保护成熟的原代OL培养物免受氧葡萄糖剥夺(OGD)。对经过OGD和hub细胞处理的OL培养物制备的RNA进行微阵列研究显示,与OL增殖、存活和修复功能(如髓鞘形成)相关的33个基因的表达增加。采用定量RT-PCR技术对以下8个基因的芯片结果进行验证:U2AF同源基元激酶1 (Uhmk1)、胰岛素诱导基因1 (Insig1)、金属硫蛋白(Mt3)、四跨蛋白2 (Tspan2)、过氧化物还氧蛋白4 (Prdx4)、stat - min样2 (Stmn2)、髓鞘少突胶质细胞糖蛋白(MOG)和versican (Vcan)。免疫组化结果显示,在大脑中动脉闭塞(MCAO)后48小时,灌注hub细胞的大鼠同侧白质束中MOG、Prdx4、Uhmk1、Insig1和Mt3蛋白表达上调。此外,对这些基因的启动子区域分析揭示了共同的转录因子结合位点,从而深入了解hub细胞激活的共享信号转导途径,以增强这些基因的转录。这些结果表明,hub细胞治疗诱导的基因表达可能对缺血具有寡保护作用。
Oligodendrocytes (OLs), the predominant cell type found in cerebral white matter, are essential for structural integrity and proper neural signaling. Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) cells protects striatal white matter tracts in vivo and directly protects mature primary OL cultures from oxygen glucose deprivation (OGD). Microarray studies of RNA prepared from OL cultures subjected to OGD and treated with HUCB cells showed an increase in the expression of 33 genes associated with OL proliferation, survival, and repair functions, such as myelination. The microarray results were verified using quantitative RT-PCR for the following eight genes: U2AF homology motif kinase 1 (Uhmk1), insulin induce gene 1 (Insig1), metallothionein ( Mt3), tetraspanin 2 (Tspan2), peroxiredoxin 4 (Prdx4), stathmin-like 2 (Stmn2), myelin oligodendrocyte glycoprotein (MOG), and versican (Vcan). Immunohistochemistry showed that MOG, Prdx4, Uhmk1, Insig1 and Mt3 protein expression were upregluated in the ipsilateral white matter tracts of rats infused with HUCB cells 48 hrs after middle cerebral artery occlusion (MCAO). Furthermore, promoter region analysis of these genes revealed common transcription factor binding sites, providing insight into the shared signal transduction pathways activated by HUCB cells to enhance transcription of these genes. These results show expression of genes induced by HUCB cell therapy that could confer oligoprotection from ischemia.
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