文章基本信息

标题：Transcriptomic profiling in human mesangial cells using patient-derived lupus autoantibodies identified miR-10a as a potential regulator of IL8
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作者：Pattarin Tangtanatakul ; Boonyakiat Thammasate ; Alain Jacquet 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-15160-8
语种：English
出版社：Springer Nature
摘要：Autoantibody-mediated inflammation directed at resident kidney cells mediates lupus nephritis (LN) pathogenesis. This study investigated the role of miRNA in human mesangial cells (HMCs) stimulated with auto anti-dsDNA immunoglobulin (Ig)G antibodies. HMCs were treated with antibodies purified from active LN patients or non-specific IgG controls in the presence of normal serum. Aberrant miRNA was screened using high throughput sequencing. Anti-dsDNA IgG up-regulated 103 miRNAs and down-regulated 30 miRNAs. The miRNAs regulated genes in the cell cycle, catabolic processes, regulation of transcription and apoptosis signalling. miR-10a was highly abundant in HMCs but was specifically downregulated upon anti-dsDNA IgG induction. Interestingly, the expression of miR-10a in kidney biopsies from class III and IV LN patients (n = 26) was downregulated compared with cadaveric donor kidneys (n = 6). Functional studies highlighted the downstream regulator of miR-10a in the chemokine signalling and cell proliferation or apoptosis pathways. Luciferase assay confirmed for the first time that IL8 was a direct target of miR-10a in HMCs. In conclusion, anti-dsDNA IgG Ab down-regulated miR-10a expression in HMCs resulting in the induction of various target genes involved in HMC proliferation and chemokine expression.