Research Resource: Nuclear Receptor Atlas of Human Retinal Pigment Epithelial Cells: Potential Relevance to Age-Related Macular Degeneration
Research Resource: Nuclear Receptor Atlas of Human Retinal Pigment Epithelial Cells: Potential Relevance to Age-Related Macular Degeneration
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DOI：
10.1210/me.2010-0392
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发表时间：
2011-02-01
影响因子：
--
通讯作者：
Malek, Goldis
中科院分区：
文献类型：
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作者：
Dwyer, Mary A.;Kazmin, Dmitri;Malek, Goldis
视网膜色素上皮(RPE)细胞在视网膜生理中起着重要的作用，它形成了血-视网膜的外部屏障，支持光感受器的功能。包括老年性黄斑变性(AMD)在内的视网膜病变涉及视网膜上皮细胞的生理和病理改变，严重损害视网膜并影响视力。核受体(NRs)，包括过氧化体增殖物激活受体和肝X受体，被认为是脂代谢紊乱和炎症等生理通路的关键调节因子，这些通路也可能参与AMD的发生发展。然而，NRs在RPE细胞中的表达水平尚未得到系统的研究。此外，细胞培养体系被广泛用于研究RPE细胞的生物学，而不知道这些体外模型和体内RPE在NR表达和活性方面的差异或相似之处。通过实时定量聚合酶链式反应，我们研究了人RPE细胞中所有48个NR家族成员加芳香烃受体和芳香烃受体核转位蛋白的表达模式。我们对新鲜分离的来自供者眼(体内)、自发生长的人类细胞系(体外)和原代细胞培养系(体外)的细胞进行了分析，以确定培养细胞系中NR表达反映体内的程度。为了评价细胞培养模型用于研究NR受体生物学的有效性，我们在体外测定了几种中高表达的NRs的转录活性和靶基因表达。最后，我们确定了在AMD的病理生物学中可能起重要作用的NRs的一个子集。(分子内分泌学25：360-372,2011)
Retinal pigment epithelial (RPE) cells play a vital role in retinal physiology by forming the outer blood-retina barrier and supporting photoreceptor function. Retinopathies including age-related macular degeneration (AMD) involve physiological and pathological changes in the epithelium, severely impairing the retina and effecting vision. Nuclear receptors (NRs), including peroxisome proliferator-activated receptor and liver X receptor, have been identified as key regulators of physiological pathways such as lipid metabolic dysregulation and inflammation, pathways that may also be involved in development of AMD. However, the expression levels of NRs in RPE cells have yet to be systematically surveyed. Furthermore, cell culture lines are widely used to study the biology of RPE cells, without knowledge of the differences or similarities in NR expression and activity between these in vitro models and in vivo RPE. Using quantitative real-time PCR, we assessed the expression patterns of all 48 members of the NR family plus aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator in human RPE cells. We profiled freshly isolated cells from donor eyes (in vivo), a spontaneously arising human cell line (in vitro), and primary cell culture lines (in vitro) to determine the extent to which NR expression in the cultured cell lines reflects that of in vivo. To evaluate the validity of using cell culture models for investigating NR receptor biology, we determined transcriptional activity and target gene expression of several moderately and highly expressed NRs in vitro. Finally, we identified a subset of NRs that may play an important role in pathobiology of AMD. (Molecular Endocrinology 25:360-372, 2011)