Overexpression of immediate early genes in active Graves' ophthalmopathy
Overexpression of immediate early genes in active Graves' ophthalmopathy
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DOI：
10.1210/jc.2004-2275
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发表时间：
2005-08-01
影响因子：
5.8
通讯作者：
Hallengren, B
中科院分区：
文献类型：
--
作者：
Lantz, M;Vondrichova, T;Hallengren, B
背景：格雷夫斯眼病的一个主要问题是眼眶内脂肪组织体积的增加。目的：这项工作的目的是确定眼眶脂肪生成的机制。设计：这是一项开放标签的前瞻性研究。背景：该研究在大学医院内分泌科诊所进行。参与者：该研究由患有视神经影响的严重眼病的患者 (n = 5) 和甲状腺健康对照者 (n = 5) 组成。 = 5).干预措施：我们对皮质类固醇无反应的患者进行了眼眶组织的侧向减压，并对甲状腺健康对照者进行了上眼睑的修复手术。主要结果测量：我们根据病例和对照中荧光强度的测定，采用微阵列技术对基因表达进行了大规模测量。结果：脂肪组织的标志物硬脂酰辅酶 A 去饱和酶在眼病中过度表达，设定选择标准有利于识别已知在正常脂肪生成中表达的基因。除了 15 个其他立即早期基因 (IEG) 之外，立即早期基因、富含半胱氨酸的血管生成诱导剂 61 (CYR61) 也过表达，并且通过 RT-PCR 证实了所选 IEG 的表达：CYR61、环氧合酶-2、双特异性磷酸酶 1、B 细胞易位基因 2 和早期生长反应 1。CYR61 反应基因，已知参与炎症、IL-1β、基质金属蛋白酶-3和血管内皮生长因子也过度表达。眼病活动期患者比慢性期患者表现出更高的 CYR61 表达，表明 CYR61 是疾病活动性的标志物。尽管所有患者均接受过皮质类固醇治疗，IL-1β的靶基因Cyclooxygenase-2也过度表达。结论：脂肪细胞相关的IEG在活动性眼病中过度表达，CYR61可能在眼眶炎症和脂肪生成中发挥作用，并可作为疾病活动性的标志物。
Context: In Graves' ophthalmopathy a major problem is an increase in the intraorbital adipose tissue volume.Objective: The aim of this work was to define mechanisms of orbital adipogenesis.Design: This was an open-label prospective study.Setting: The study was conducted at the Clinic of Endocrinology, University Hospital.Participants: The study consisted of patients (n = 5) with severe ophthalmopathy with affection of the optic nerve and thyroid healthy controls (n = 5).Interventions: We performed lateral decompression of orbital tissue in patients unresponsive to corticosteroids and restorative surgery of the upper eyelid in thyroid healthy controls.Main Outcome Measure: We made large-scale measurements of gene expression, with microarray technique based on determination of fluorescence intensities in cases and controls.Results: A marker of adipose tissue, stearoyl-coenzyme A desaturase, was overexpressed in ophthalmopathy, and selection criteria were set to favor identification of genes known to be expressed in normal adipogenesis. The immediate early gene, cysteine-rich, angiogenic inducer, 61 (CYR61), was overexpressed in addition to 15 other immediate early genes (IEGs), and the expression of selected IEGs was confirmed with RT-PCR: CYR61, cyclooxygenase-2, dual-specificity phosphatase 1, B cell translocation gene 2, and early growth response 1. CYR61-responsive genes, known to participate in inflammation, IL-1 beta, matrix metalloproteinase-3, and vascular endothelial growth factor were also overexpressed. Patients showed greater expression of CYR61 in the active than the chronic phase of ophthalmopathy, indicating that CYR61 is a marker of disease activity. Cyclooxygenase-2, the target gene of IL-1 beta, was also overexpressed, although all patients had been treated with corticosteroids.Conclusion: Adipocyte-related IEGs are overexpressed in active ophthalmopathy, and CYR61 may have a role in both orbital inflammation and adipogenesis and serve as a marker of disease activity.