Abstract
Systemic lupus erythematosus (SLE) is a common autoimmune disease with high incidence in females. The pathogenesis of SLE is complex, and healing SLE has become a serious challenge for clinical treatment. Aberrant expression of miR-301a-3p involves the progressions of multiple diseases, and some studies have indicated that increased miR-301a-3p could induce the inflammatory injury of some organs. However, the role and molecular mechanism of miR-301a-3p in SLE remain unclear. In this study, the miR-301a-3p levels in peripheral blood mononuclear cells (PBMCs) of the patients with SLE and health subjects were measured with qRT-PCR. The ELISA assay was used to investigate the effect of miR-301a-3p on the levels of inflammatory factors in PBMCs, and flow cytometry assays were used to observe the effect of miR-301a-3p on the levels of CD4+ T cells and Th17 cells in PBMCs. Moreover, TargetScan, dual-luciferase reporter assay, and western blot were used to reveal the downstream targets and regulation mechanism of miR-301a-3p in SLE. The results showed that miR-301a-3p was significantly upregulated in PBMCs of the SLE patients, and increased miR-301a-3p could boost the expression of IL-6, IL-17, and INF-γ in PBMCs and promote the differentiation of Th17 cells. It was found that PELI1 was a target of miR-301a-3p, and PELI1 upregulation could effectively reverse the effect of miR-301a-3p on PBMCs. Besides, this study also found that miR-301a-3p could promote the expression of IRAK1 to involve the progression of SLE via targeting PELI1. In conclusion, this study suggests that increased miR-301a-3p serves as a pathogenic factor in SLE to promote IRAK1-mediated differentiation of Th17 cells via targeting PELI1.
Highlights
IntroductionSystemic lupus erythematosus (SLE) is a common autoimmune disease which always involves the complications, such as the injury of skin, joints, and multiple organs [1, 2]
Systemic lupus erythematosus (SLE) is a common autoimmune disease which always involves the complications, such as the injury of skin, joints, and multiple organs [1, 2].e incidence of SLE is increasing year by year
To investigate the relationship of miR-301a-3p and SLE, the qRT-PCR was performed to evaluate the abundance of miR-301a-3p in peripheral blood mononuclear cells (PBMCs) of the patients with SLE and health subjects. e study indicated that miR-301a-3p was obviously upregulated in the PBMCs of the patients (Figure 1, P < 0.01). is proof suggested that miR-301a-3p upregulation is related with the progression of SLE
Summary
Systemic lupus erythematosus (SLE) is a common autoimmune disease which always involves the complications, such as the injury of skin, joints, and multiple organs [1, 2]. E incidence of SLE is increasing year by year. Increased CD4+ T cells have been confirmed as a marked event for SLE development [4]. The symptoms SLE are complicated and recurrent, confounding attempts to determine the cause and develop effective methods for this disease. Increasing studies have revealed that the dysfunctions of some miRNAs involve the development and deterioration of the autoimmune diseases [7, 8]. Several researches have indicated that miRNA profiling of the patients with SLE may exhibit obvious difference compared with that of the healthy persons. The study has indicated that miR-125b was significantly downregulated in the serums of the patients with SLE, and Journal of Healthcare Engineering increased miR-125b could inhibit the autograph of peripheral blood mononuclear cells (PBMCs) to suppress the progression of SLE via directly targeting UVRAG [9]
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