Decreased microRNA(miR)-145 and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis
Journal
Clinical and Experimental Immunology
Journal Volume
171
Journal Issue
1
Pages
91-99
Date Issued
2013
Author(s)
Abstract
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed miRNAs using real-time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant-expressed miRNAs was detected using real-time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR-145, miR-224, miR-513-5p, miR-150, miR-516a-5p, miR-483-5p and miR-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed miR-145 and over-expressed miR-224 were noted. We further found that STAT1 mRNA targeted by miR-145 was over-expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with miR-145 suppressed STAT1 and miR-224 transfection suppressed API5 protein expression. Over-expression of miR-224 facilitates activation-induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR-145 and miR-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation-induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription-1 (STAT)-1 expression in patients with SLE. ? 2012 British Society for Immunology.
Subjects
API5; MiR-145; MiR-224; STAT-1; Systemic lupus erythematosus
SDGs
Other Subjects
azathioprine; cyclosporin; hydroxychloroquine; messenger RNA; methylprednisolone; microRNA; microRNA 145; microrna 150; microRNA 224; microRNA 483 5p; microRNA 513 5p; microRNA 516a 5p; microRNA 629; mycophenolic acid; neuronal apoptosis inhibitory protein; neuronal apoptosis inhibitory protein 5; STAT1 protein; unclassified drug; adult; article; clinical article; controlled study; female; flow cytometry; gene expression; genetic transfection; human; human cell; immunopathogenesis; lupus erythematosus nephritis; male; priority journal; protein expression; real time polymerase chain reaction; systemic lupus erythematosus; T lymphocyte; Adult; Apoptosis; Apoptosis Regulatory Proteins; Female; Humans; Jurkat Cells; Lupus Erythematosus, Systemic; Male; MicroRNAs; Middle Aged; Nuclear Proteins; STAT1 Transcription Factor; T-Lymphocytes; Transcriptome; Transfection
Type
journal article