Tseng Ling-Hong, Chen Ilene, Wang Chao-Nin, Lin Yi-Hao, Lloyd L Keith, Lee Chyi-Long
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, School of Medicine, Kwei-Shan, Tao-Yuan, Taiwan.
Int Urogynecol J. 2010 Aug;21(8):911-8. doi: 10.1007/s00192-010-1129-x. Epub 2010 Mar 4.
The aim of this study was to explore potential molecular mechanisms contributing to the pathogenesis of Hunner's ulcer type interstitial cystitis (IC).
Dataset acquisitions from Gene Expression Omnibus under platform accession no GSE 11783. We compared global gene expression profiles in bladder epithelial cells from IC patients with Hunner's ulcer corresponding to normal controls. We re-sampling and exploit the correlation structure presented in the dataset through the transcriptional response. For each patient, two bladder biopsies were studied, one from an ulcer area and one from a non-ulcer area. RNA was extracted, and all labeled samples were hybridized to Human Genome U133 Plus 2.0 Array (Affymetrix, CA, USA).
The Mahalanobis distance in hierarchical cluster analysis revealed a model of 40 genes expression which is increased in IC and ulcerated IC. Our results can be summarized as follows: First, the expressions of major histocompatibility complex (MHC) class IF and II molecules, leukocyte immunoglobulin-like receptors, hepatitis A virus cellular receptor 2, and interleukin 32 were increased in bladder epithelial from IC and ulcerative IC area. Next, there is an indication of antigen-mediated aggregation of the high-affinity Fc epsilon and gamma RI leading to allergic inflammation through the disease status. Third, the high-affinity Fc gamma RI subunit facilitated T-cell-mediated immune response through the disease status. Such changes, jointly termed "bladder remodeling," can constitute an important long-term consequence of Hunner's ulcer type IC.
Our results indicate that genome-based expression profiling can be used for the diagnostic tests of Hunner's ulcer type IC in clinical practice.
本研究旨在探索与间质性膀胱炎（IC）中Hunner溃疡发病机制相关的潜在分子机制。
从基因表达综合数据库（Gene Expression Omnibus）获取平台登录号为GSE 11783的数据集。我们比较了患有Hunner溃疡的IC患者膀胱上皮细胞与正常对照的整体基因表达谱。我们通过转录反应对数据集进行重采样并利用其中呈现的相关结构。对于每位患者，研究了两块膀胱活检组织，一块来自溃疡区域，一块来自非溃疡区域。提取RNA，所有标记样本与人类基因组U133 Plus 2.0芯片（美国加利福尼亚州Affymetrix公司）进行杂交。
层次聚类分析中的马氏距离揭示了一个40个基因表达的模型，该模型在IC和溃疡性IC中表达增加。我们的结果可总结如下：首先，主要组织相容性复合体（MHC）I类和II类分子、白细胞免疫球蛋白样受体、甲型肝炎病毒细胞受体2和白细胞介素32在IC和溃疡性IC区域的膀胱上皮中的表达增加。其次，有迹象表明高亲和力Fcε和γRI的抗原介导聚集通过疾病状态导致过敏性炎症。第三，高亲和力FcγRI亚基通过疾病状态促进T细胞介导的免疫反应。这些变化统称为“膀胱重塑”，可能构成Hunner溃疡型IC的重要长期后果。
我们的结果表明，基于基因组的表达谱分析可用于临床实践中Hunner溃疡型IC的诊断测试。
