Gene expression profiling of orbital adipose tissue from patients with graves' ophthalmopathy: A potential role for secreted frizzled-related protein-1 in orbital adipogenesis
Gene expression profiling of orbital adipose tissue from patients with graves' ophthalmopathy: A potential role for secreted frizzled-related protein-1 in orbital adipogenesis
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DOI：
10.1210/jc.2004-2239
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发表时间：
2005-08-01
影响因子：
5.8
通讯作者：
Bahn, RS
中科院分区：
文献类型：
--
作者：
Kumar, S;Leontovich, A;Bahn, RS
内容：Graves眼病（GO）的体征和症状是由于炎症和眼眶脂肪组织和眼外肌体积增加引起的。目的：我们的目的是鉴定可能参与刺激GO中所见的眼眶脂肪组织扩张的差异调节基因。设计：基因表达谱用于比较GO患者和正常个体眼眶脂肪组织中表达的基因。该研究在一家私人诊所三级转诊中心进行。患者：眼眶脂肪组织是在经窦眼眶减压手术中从20名因严重GO而接受此手术的甲状腺功能正常的患者中收集的，并在早期尸检中从8名没有甲状腺或眼部疾病证据的正常人中收集的。在分析的12，686个基因中，25个已知基因在GO眼眶组织中表达增加（> 4倍），而11个基因表达减少（> 4倍）。通过定量RT-PCR证实的上调基因包括分泌型卷曲相关蛋白-1（sFRP-1; 18.5倍）和几种脂肪细胞相关基因，包括过氧化物酶体增殖物激活受体-γ（44.1倍）和脂联素（25倍）。在体外用重组sFRP-1（100 nM）处理GO眼眶前脂肪细胞显著增加脂联素（2.0倍; P < 0.05），瘦素（7倍; P < 0.002），TSH受体mRNA（13倍; P < 0.003）的水平和增强的油红-O染色。这些结果支持了在GO中眼眶脂肪形成增强的概念，并表明GO眼眶中sFRP-1水平升高可能参与刺激该致病过程。
Context: The signs and symptoms of Graves' ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles.Objective: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO.Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals.Setting: The study took place at a private practice tertiary referral center.Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease.Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (> 4-fold) in GO orbital tissues, whereas 11 genes were decreased (> 4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-gamma(44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 ( 100 nM) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures.Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.