Duration of chronic inflammation alters gene expression in muscle from untreated girls with juvenile dermatomyositis.
Duration of chronic inflammation alters gene expression in muscle from untreated girls with juvenile dermatomyositis.
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DOI：
10.1186/1471-2172-9-43
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发表时间：
2008-07-31
期刊：
影响因子：
3
通讯作者：
Pachman LM
中科院分区：
文献类型：
--
作者：
Chen YW;Shi R;Geraci N;Shrestha S;Gordish-Dressman H;Pachman LM
为了评估慢性炎症持续时间对未经治疗的幼年型皮肌炎(JDM)儿童骨骼肌活检(MBX)基因表达的影响，并确定与疾病进展相关的基因和生物学过程，对16名JDM活动症状大于或等于2个月的女孩和3名活动症状小于2个月的女孩的表达谱数据进行了比较。79个基因在未经治疗的疾病持续时间长或短的组之间有差异表达。在症状大于或等于2个月的儿童的肌肉活检中，参与免疫反应和血管重塑的基因表达水平较高，而参与应激反应和蛋白质周转的基因表达水平较低。在79个基因中，9个基因的表达与初治病程呈显著的线性回归关系。定量RT-PCR验证了5个差异表达基因：人类白细胞抗原-DQA1、肌球蛋白重链、聚集素、网织蛋白D1和肌腱调节蛋白。免疫组织化学证实，病程较长的慢性炎症与DC-LAMP+和BDCA2+成熟树突状细胞的增加有关。我们的结论是，慢性炎症改变了未经治疗的JDM儿童肌肉中的基因表达模式。持续时间大于或等于2个月的症状与树突状细胞成熟和抗血管新生血管重塑有关，直接导致疾病的病理生理学。
To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater than or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodelling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes – HLA-DQA1, smooth muscle myosin heavy chain, clusterin, plexin D1 and tenomodulin – were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology.
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DOI：
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发表时间：
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期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
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