Department of Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
PLoS One. 2010 May 11;5(5):e10344. doi: 10.1371/journal.pone.0010344.
MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression. In this study we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in peripheral blood mononuclear cells (PBMCs) and Epstein-Barr Virus (EBV)-transformed cell lines obtained from lupus nephritis affected patients and unaffected controls. TaqMan-based stem-loop real-time polymerase chain reaction was used for validation. Microarray analysis of miRNA expressed in both African American (AA) and European American (EA) derived lupus nephritis samples revealed 29 and 50 differentially expressed miRNA, respectively, of 850 tested. There were 18 miRNA that were differentially expressed in both racial groups. When samples from both racial groups and different specimen types were considered, there were 5 primary miRNA that were differentially expressed. We have identified 5 miRNA; hsa-miR-371-5P, hsa-miR-423-5P, hsa-miR-638, hsa-miR-1224-3P and hsa-miR-663 that were differentially expressed in lupus nephritis across different racial groups and all specimen types tested. Hsa-miR-371-5P, hsa-miR-1224-3P and hsa-miR-423-5P, are reported here for the first time to be associated with lupus nephritis. Our work establishes EBV-transformed B cell lines as a useful model for the discovery of miRNA as biomarkers for SLE. Based on these findings, we postulate that these differentially expressed miRNA may be potential novel biomarkers for SLE as well as help elucidate pathogenic mechanisms of lupus nephritis. The investigation of miRNA profiles in SLE may lead to the discovery and development of novel methods to diagnosis, treat and prevent SLE.
MicroRNAs (miRNA) 已成为调节基因表达的一类重要的新调节剂。在这项研究中，我们研究了狼疮肾炎中差异表达的 miRNA。我们使用微阵列技术研究了来自狼疮肾炎患者和未受影响对照的外周血单个核细胞 (PBMC) 和 Epstein-Barr 病毒 (EBV) 转化细胞系中差异表达的 miRNA。使用 TaqMan 基于茎环实时聚合酶链反应进行验证。对来自非裔美国人和欧洲裔美国人（EA）的狼疮肾炎样本中表达的 miRNA 进行微阵列分析，分别显示 850 个测试 miRNA 中有 29 个和 50 个差异表达。有 18 个 miRNA 在两个种族群体中均有差异表达。当考虑两个种族群体的样本和不同的标本类型时，有 5 个主要的 miRNA 存在差异表达。我们已经确定了 5 个 miRNA；hsa-miR-371-5P、hsa-miR-423-5P、hsa-miR-638、hsa-miR-1224-3P 和 hsa-miR-663，它们在不同种族群体和所有测试的标本类型中均在狼疮肾炎中差异表达。hsa-miR-371-5P、hsa-miR-1224-3P 和 hsa-miR-423-5P，这是首次报道它们与狼疮肾炎有关。我们的工作建立了 EBV 转化的 B 细胞系作为发现 miRNA 作为 SLE 生物标志物的有用模型。基于这些发现，我们推测这些差异表达的 miRNA 可能是 SLE 的潜在新型生物标志物，并有助于阐明狼疮肾炎的发病机制。SLE 中 miRNA 谱的研究可能会导致发现和开发新的方法来诊断、治疗和预防 SLE。
