The role of miR-146a in modulating TRAF6-induced inflammation during lupus nephritis

C.-Z. Zheng, Y.-B. Shu, Y.-L. Luo, J. Luo

Department of Nephropathy, Traditional Chinese Hospital of Lu’an, Lu’an, Anhui Province, China. changzhizheng123@163.com

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• Nephrology

OBJECTIVE: Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). A previous study showed decreased expression level of microRNA (miR)-146a in LN patients, indicating its possible role in LN pathogenesis.

PATIENTS AND METHODS: A total of 98 LN patients were recruited, for the collection of renal tissue samples during biopsy or surgery. Another cohort of 15 patients who had renal tumor resection was recruited as the control group, for the further comparison of expression levels of miR-146a, TRAF6 and p-p65 in tissues. Human glomerular mesangial cells were treated with miR-146a mimics, si-TRAF6 or both, followed by the evaluation of p65, p-p65, IL-1β, IL-6, IL-8 and TNF-α. Transwell assay was performed to detect the effect of mesangial cells on chemotaxis of macrophage.

RESULTS: MiR-146a expression was significantly depressed in renal tissues of LN patients, while TRAF6 expression, macrophage infiltration and p-p65 expression were all elevated as the activity of LN was induced. The up-regulation of miR-146a and/or down-regulation of TRAF6 can significantly inhibit NF-κB transcriptional activity of glomerular mesangial cells, while the gene expressions of IL-1β, IL-6, IL-8 and TNF-α were suppressed.

CONCLUSIONS: The expression of miR-146a in renal tissues of LN patients was significantly depressed, while the transcriptional activity of TRAF6 and NF-κB was enhanced. MiR-146 thus inhibited NF-κB transcriptional activity and inflammatory factor synthesis, and alleviated chemotactic effect towards macrophage via the inhibition of TRAF6 activity.

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