Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy.
Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy.
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DOI：
10.1002/ana.21805
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发表时间：
2010-01
影响因子：
11.2
通讯作者：
Greenberg, Steven A.
中科院分区：
文献类型：
--
作者：
Salaiegheh, Mohammad;Kong, Sek Won;Pinkus, Jack L.;Walsh, Ronan J.;Liao, Anne;Nazareno, Remedios;Amato, Anthony A.;Krastins, Bryan;Morehouse, Chris;Higgs, Brandon W.;Jallal, Bahlia;Yao, Yihong;Sarracino, David A.;Parker, Kenneth C.;Greenberg, Steven A.
皮肌炎（DM）是一种累及肌肉和皮肤的自身免疫性疾病。肌纤维束周萎缩（PFA）是糖尿病特有的病理改变。干扰素刺激基因15（Interferon-stimulated gene 15，ISG 15）是一种泛素样修饰物，其免疫学作用知之甚少。我们生成了微阵列数据，测量了113个人类肌肉活检标本中每个标本中大约18，000个基因的表达。活检标本和培养的骨骼肌进行了进一步研究，采用免疫组化，免疫印迹，蛋白质组分析液相色谱/质谱，实时定量PCR，激光捕获显微切割。编码ISG 15缀合途径蛋白的转录物在患有PFA的DM（DM-PFA）肌肉中上调，在所有DM-PFA患者中存在ISG 15（339倍）、HERC 5（62倍）和USP 18（68倍）的显著升高，但在99个非DM样品中没有。与公开可用的微阵列数据集的组合分析进一步显示，与来自广泛肌肉疾病的199个其他肌肉样本相比，来自成人DM-PFA和青少年DM的28个活检样本的显著ISG 15和USP 18转录物升高具有100%的灵敏度和特异性。通过免疫印迹仅在DM-PFA肌肉中发现游离ISG 15和ISG 15缀合的蛋白。培养的人骨骼肌暴露于1型干扰素产生类似的成绩单和ISG 15蛋白和ISG 15共轭物。激光捕获显微切割后的蛋白质组学分析表明，肌联蛋白缺乏DM束周萎缩肌纤维。对来自不同肌肉疾病集合的肌肉样本的大规模微阵列研究显示，自身免疫性疾病皮肌炎与ISG 15缀合途径的过度激活独特相关。人骨骼肌细胞培养物暴露于1型干扰素产生的分子图像与人DM肌肉活检标本的分子图像高度相似。糖尿病患者的束周萎缩肌纤维缺乏许多骨骼肌蛋白，最明显的是肌联蛋白。
Dermatomyositis (DM) is an autoimmune disease involving muscle and skin. Perifascicular atrophy (PFA) of myofibers is a specific and characteristic DM pathological lesion. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like modifier with a poorly understood immunological role. We generated microarray data measuring the expression of approximately 18,000 genes in each of 113 human muscle biopsy specimens. Biopsy specimens and cultured skeletal muscle were further studied using immunohistochemistry, immunoblotting, proteomic profiling by liquid chromatography/mass spectrometry, real-time quantitative PCR, and laser capture microdissection. Transcripts encoding ISG15-conjugation pathway proteins were upregulated in DM with PFA (DM-PFA) muscle, with marked elevation of ISG15 (339-fold), HERC5 (62-fold), and USP18 (68-fold) present in all DM-PFA patients but none of 99 non-DM samples. Combined analysis with publicly available microarray datasets further showed marked ISG15 and USP18 transcript elevation had 100% sensitivity and specificity for 28 biopsies from adult DM-PFA and juvenile DM compared to 199 other muscle samples from a wide range of muscle diseases. Free ISG15 and ISG15-conjugated proteins were found by immunoblot only in DM-PFA muscle. Cultured human skeletal muscle exposed to type 1 interferons produced similar transcripts and both ISG15 protein and ISG15 conjugates. Laser capture microdissection followed by proteomic analysis showed deficiency of titin in DM perifascicular atrophic myofibers. A large-scale microarray study of muscle samples from a diverse collection of muscle diseases revealed that the autoimmune disease dermatomyositis was uniquely associated with overactivation of the ISG15 conjugation pathway. Exposure of human skeletal muscle cell culture to type 1 interferons produces a molecular picture highly similar to that of human DM muscle biopsy specimens. Perifascicular atrophic myofibers in DM are deficient in a number of skeletal muscle proteins, most markedly titin.
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影响因子：
3.4
作者：
Parker, Kenneth C.;Kong, Sek Won;Walsh, Ronan J.;Salajegheh, Mohammad;Moghadaszadeh, Behzad;Amato, Anthony A.;Nazareno, Remedios;Lin, Yin Yin;Krastins, Bryan;Sarracino, David A.;Beggs, Alan H.;Pinkus, Jack L.;Greenberg, Steven A.
通讯作者：
Greenberg, Steven A.
影响因子：
15.9
作者：
Peterson, KS;Huang, JF;Winchester, RJ
通讯作者：
Winchester, RJ
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
2.7
作者：
Peng, J.;Raddatz, K.;Gotthardt, M.
通讯作者：
Gotthardt, M.
DOI：
10.1016/j.bbrc.2005.08.132
发表时间：
2005-10-21
影响因子：
3.1
作者：
Giannakopoulos, NV;Luo, JK;Zhang, DE
通讯作者：
Zhang, DE