Elevated Serum Inflammatory Cytokines in Lupus Nephritis Patients, in Association with Promoted hsa-miR-125a.

Abstract

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, human systemic autoimmune disease characterized by autoantibody formation. MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression and have been confirmed to regulate the lymphocyte tolerance and autoimmunity in SLE. In this study, we investigated the serum miRNA profile in lupus nephritis (LN) patients with microarray technology. TaqMan-based stem-loop real-time polymerase chain reaction was used for validation. We also examined the serum cytokines and chemokines, such as IL-β, IL-6, TNF-β, and IP-10, and then analyzed the association of the upregulated IL-β, IL-6, TNF-α, and IP-10 with each miRNA. Microarray analysis of miRNA indicated 17 upregulated miRNAs in LN patients. Such upregulation of hsa-miR-150, hsa-miR-200c, hsa-miR-181a, hsa-miR-125a, and hsa-miR-675 was also confirmed by RT-qPCR. We also recognized the significant upregulation of serum IL-β, IL-6, TNF-α, and IP-10 in those LN patients. Moreover, the upregulated IL-β, IL-6, and TNF-α was significantly associated with serum hsa-miR-125a. Our study recognized the upregulation of miRNAs such as hsa-miR-150, hsa-miR-200c, hsa-miR-181a, hsa-miR-125a, and hsa-miR-675 and the upregulation of such cytokines and chemokines as IL-β, IL-6, TNF-α, and IP-10. The upregulated miR-125a contributed to the upregulation of inflammatory IL-β, IL-6, and TNF-α in LN. Our findings demonstrate that miR-125a can be a novel biomarker for SLE, and help elucidate pathogenic mechanisms of lupus nephritis.