Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human
Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human
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DOI：
10.1016/j.exer.2004.08.022
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发表时间：
2004-12-01
影响因子：
3.4
通讯作者：
Goldstein, LE
中科院分区：
文献类型：
--
作者：
Chylack, LT;Fu, L;Goldstein, LE
透镜上皮衍生生长因子（LEDGF/p75）是一种新型的转录辅激活因子，在透镜上皮细胞基因调控和应激反应中起重要作用。最近的证据表明LEDGF/p75可能在透镜上皮细胞向纤维细胞终末分化中起重要作用。由于透镜和大脑都是由上皮样祖细胞产生的外胚层衍生器官，我们假设LEDGF/p75在两个器官中表达并具有相似的功能。为了研究这一假设，我们研究了LEDGF/p75在人脑中的表达和定位。我们检测LEDGF/p75特异性RT-PCR反应产物在胎儿和成人大脑。脑内LEDGF/p75 mRNA的表达具有不同的发育和区域特异性。LEDGF/p75基因在胎儿脑中的表达明显高于成人脑。在成人脑中，LEDGF/p75 mRNA的表达是大量的脑室下区（SVZ），海马很少，和其他地方检测不到。为了研究LEDGF/p75蛋白的表达和定位，我们开发并纯化了一种新的抗LEDGF/p75多克隆抗体，该抗体针对LEDGF/p75的独特C-末端区域。对胎儿和成人脑组织的Western印迹分析显示了一个类似于75 kDa的蛋白质，该蛋白质表现出与RT-PCR分析相似的发育和区域特异性。LEDGF/p75蛋白在胎儿脑和成人SVZ中表达较高。免疫组织化学研究显示，人胎脑的LEDGF/p75免疫反应阳性细胞在生殖神经上皮和皮质板区域。成人和老年人的大脑分析显示LEDGF/p75免疫反应阳性细胞富集在SVZ毗邻的腹侧区的侧脑室的水平的前连合，一个区域参与成人神经发生。我们利用原代混合皮质细胞培养系统来鉴定神经元中的LEDGF/p75，但不鉴定星形胶质细胞。神经元LEDGF/p75主要分布于核周。这些数据表明，LEDGF/p75在胎儿和成人脑内的离散区域和细胞类型中表达。此外，LEDGF/p75的发育和区域表达模式表明，这种转录共激活因子可能参与神经上皮干细胞分化和神经发生。(C)2004爱思唯尔有限公司保留所有权利。
Lens epithelium-derived growth factor (LEDGF/p75) is a novel transcription co-activator that is critically involved in lens epithelial cell gene regulation and stress responses. Recent evidence indicates that LEDGF/p75 may play an important role in lens epithelial to fibre cell terminal differentiation. Since the lens and the brain are both ectodermally derived organs generated from epithelioid progenitor cells, we hypothesize that LEDGF/p75 is expressed and subserving similar functions in both organs. To investigate this hypothesis, we studied LEDGF/p75 expression and localization in the human brain. We detected LEDGF/p75-specific RT-PCR reaction products in both fetal and adult human brain. LEDGF/p75 mRNA expression in the brain exhibited differential developmental and regional specificity. LEDGF/p75 transcript was markedly elevated in fetal as compared to adult brain. In the adult brain, LEDGF/p75 mRNA expression was substantial in the subventricular zone (SVZ), scant in hippocampus, and undetectable elsewhere. To study LEDGF/p75 protein expression and localization, we developed and purified a new anti-LEDGF/p75 polyclonal antibody directed against a unique C-terminal region of LEDGF/p75. Western blot analysis of fetal and adult human brain revealed a similar to75 kDa protein that demonstrated developmental and regional specificity similar to that detected by RT-PCR analysis. LEDGF/p75 protein expression was high in fetal brain and in the adult SVZ. Immunohistochemical studies of human fetal brain showed prominent LEDGF/p75-immunoreactive cells in the germinal neuroepithelium and cortical plate regions. Analysis of adult and aged human brain revealed LEDGF/p75-immunoreactive cell enrichment in the SVZ adjacent to the ventral region of the lateral ventricle at the level of the anterior commisure, a region implicated in adult neurogenesis. We utilised a primary mixed cortical cell culture system to identify LEDGF/p75 in neurons, but not astrocytes. Neuronal LEDGF/p75 exhibited a predominantly perinuclear distribution pattern. These data demonstrate that LEDGF/p75 is expressed in discrete regions and cell types within the fetal and adult human brain. Moreover, the developmental and regional expression patterns of LEDGF/p75 suggest that this transcriptional co-activator may be involved in neuroepithelial stem cell differentiation and neurogenesis. (C) 2004 Elsevier Ltd. All rights reserved.