title: Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus.
abstract: BACKGROUND
  Recent reports have shown that microRNAs (miRNAs) regulate vital immunological processes and have emerged as key regulators of immune system development and function. Therefore, it is important to determine miRNA dysregulation and its pathogenic contribution in autoimmune diseases, an aspect not adequately addressed thus far.
  
  
  RESULTS
  In this study, we profiled miRNA expressions in splenic lymphocytes from three murine lupus models (MRL-lpr, B6-lpr and NZB/W(F₁)) with different genetic background by miRNA microarray assays and Real-time RT-PCR. Despite the genetic differences among these three lupus stains, a common set of dysregulated miRNAs (miR-182-96-183 cluster, miR-31, and miR-155) was identified in splenocytes when compared with age-matched control mice. The association of these miRNAs with the disease was highlighted by our observation that this miRNA expression pattern was evident in NZB/W mice only at an age when lupus disease is manifested. Further, we have shown that the miRNA dysregulation in MRL-lpr mice was not simply due to the activation of splenocytes. By Real-time RT-PCR, we confirmed that these miRNAs were upregulated in both purified splenic B and T cells from MRL-lpr mice. miR-127 and miR-379, which were greatly upregulated in splenocytes from lpr mice, were moderately increased in diseased NZB/W mice. In addition, Real-time RT-PCR revealed that miR-146a, miR-101a, and miR-17-92 were also markedly upregulated in splenic T, but not B cells from MRL-lpr mice.
  
  
  CONCLUSIONS
  The identification of common lupus disease-associated miRNAs now forms the basis for the further investigation of the pathogenic contribution of these miRNAs in autoimmune lupus, which will advance our knowledge of the role of miRNAs in autoimmunity. Given that miRNAs are conserved, with regard to both evolution and function, our observation of a common lupus disease-associated miRNA expression pattern in murine lupus models is likely to have significant pathogenic, diagnostic, and/or therapeutic implications in human lupus.
authors.affiliation: Center for Molecular Medicine and Infectious Diseases (CMMID), Department of Biomedical Sciences and Pathology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America. rdai05@vt.edu
authors.forename: Rujuan
authors.initials: R
authors.lastname: Dai
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Deena
authors.initials: D
authors.lastname: Khan
authors.forename: Bettina
authors.initials: B
authors.lastname: Heid
authors.forename: David
authors.initials: D
authors.lastname: Caudell
authors.forename: Oswald
authors.initials: O
authors.lastname: Crasta
authors.forename: S Ansar
authors.initials: SA
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D035683:MicroRNAs