Regulation of MiR-146a and TRAF6 in the Diagnose of Lupus Nephritis

Abstract

BackgroundLupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). This study tested miR-146a and its target gene TRAF6 expression in LN patients and discussed their relationship with LN.Material/MethodsOne hundred twenty-eight LN patients and 30 healthy controls were enrolled in this study. MiR-146a and TRAF6 expression in peripheral blood mononuclear cells (PBMCs) were detected. Serum cytokines content was determined by ELISA. The diagnostic role of miR-146a and TRAF6 in LN activity was evaluated by ROC curve. The impact of miR-146a and TRAF6 on end-stage renal disease (ESRD) was compared by survival curve. The effect of miR-146a and TRAF6 on LN recurrence was analyzed.ResultsCompared with healthy controls, miR-146a expression was significantly reduced and TRAF6 was upregulated in LN patients. The expression was related to LN activity. MiR-146a expression was negatively correlated, whereas TRAF6 was positively correlated with serum IL-1β, IL-6, IL-8, and TNF-α activity. The area under the ROC curve (AUC) of miR-146a and TRAF6 on the diagnosis of LN was 0.821 and 0.897, respectively. The AUC of miR-146a and TRAF6 on LN activity differentiation was 0.921 and 0.872, respectively. Downregulation of miR-146a and upregulation of TRAF6 increased the incidence of ESRD progression. Downregulation of miR-146a and upregulation of TRAF6 elevated the possibility of recurrence within one year.ConclusionsMiR-146a declined, while TRAF6 increased in LN patients compared with healthy controls. Their expression can be used to effectively differentiate LN and evaluate activity. MiR-146a reduction and TRAF6 upregulation increased the possibility of ESRD progress and recurrence within one year.

Diagnostic significance of circulating miRNAs in systemic lupus erythematosus

“…However, five articles were excluded by reading their complete articles due to article types, seven studies lacked available data to construct a 2×2 table, and four articles lacked a comparison between SLE patients and healthy controls. Finally, 17 studies [17][18][19][20][21][31][32][33][34][35][36][37][38][39][40][41][42] were included in the meta-analysis. The process of study selection was illustrated in Fig 1. Except the study of Zununi Vahed et al [42] is a cross-sectional trial, all others are prospective trials.…”

“…Additionally, the ideal time for specimen acquisition was before treatment. Unfortunately, only two of the studies [17,31] involved in our meta-analysis indicated that blood samples were collected before treatment, while six studies [20,33,37,39,40,42] did not clarify when the specimens were obtained, five studies [18,19,21,36,41] stated that samples were collected during the period of treatments, and four articles [32,34,35,38] indicated that the time for specimen collection was after the patients had stopped treatments for a period of time. Thus, these differences in patient and blood collection time could cause inevitable bias to our results.…”

Circulating Exosomes Derived-miR-146a from Systemic Lupus Erythematosus Patients Regulates Senescence of Mesenchymal Stem Cells

“…The level of miR-146a was obviously downregulated in the PBMCs of SLE patients, and it could restrain the expression and secretion of IL-1 β , IL-6, IL-8, and TNF- α [32]. It negatively regulated NF- κ B signaling pathway and inflammatory reaction activation through targeting TRAF6 [33]. In this study, we observed that serum exosomal miR-146a was decreased in 10 SLE patients in a miRNA level.…”

Mechanism by which TRAF6 Participates in the Immune Regulation of Autoimmune Diseases and Cancer

“…TRAF6 is positively correlated with serum IL-1 β , IL-6, IL-8, and TNF- α activities. miR-146a reduction and TRAF6 upregulation increase the likelihood of the progression and recurrence of end-stage renal disease (ESRD) within one year [ 97 ]. Interestingly, miR-146a is enriched in urinary exosomes in patients with LN [ 98 ].…”