Transcriptomic profiling in human mesangial cells using patient-derived lupus autoantibodies identified miR-10a as a potential regulator of <i>IL8</i>

Tangtanatakul, Pattarin, Thammasate, Boonyakiat, Jacquet, Alain, Reantragoon, Rangsima, Pisitkun, Trairak ORCID: 0000-0001-6677-2271, Avihingsanon, Yingyos, Leelahavanichkul, Asada and Hirankarn, Nattiya (2017) Transcriptomic profiling in human mesangial cells using patient-derived lupus autoantibodies identified miR-10a as a potential regulator of <i>IL8</i>. SCIENTIFIC REPORTS, 7 (1). 14517-. ISSN 2045-2322, 2045-2322

Access the full-text of this item by clicking on the Open Access link.

Official URL: https://doi.org/10.1038/s41598-017-15160-8

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Lupus Nephritis, Immunoglobulin G, MicroRNAs, RNA, Messenger, Interleukin-8, Interleukin-6, Autoantibodies, Gene Expression Profiling, Gene Expression Regulation, Adult, Female, Male, Mesangial Cells
Depositing User:	Symplectic Admin
Date Deposited:	21 Feb 2020 10:59
Last Modified:	07 Dec 2024 01:13
DOI:	10.1038/s41598-017-15160-8
Open Access URL:	http://doi.org/10.1038/s41598-017-15160-8
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3076024