Background and aims Type 1 interferon(IFN) is a critical pathogenic factor in Systemic Lupus Erythematosus(SLE) and its associated nephritis, as elevated IFN inducible genes have been found in the kidney tissues and deficiency of IFN receptor protects lupus mouse model from developing nephritis. In this study, we want to find if there are miRNAs abnormal in the kidneys of lupus patients.
Methods miRNAs were quantified by RT-qPCR. Interferon-stimulated response element(ISRE)-luciferase reporter assay and western blotting were used to investigate the function of candidate miRNAs. Genes that were affected by specific miRNA were identified by microarray. Antagomir(chemical modified miRNA inhibitors) was used to inhibit the function of candidate miRNA to validate its function. We administrated agomir(chemical modified miRNA mimics) into pristane induced pulmonary haemorrhage(PH) mouse model to investigate the in vivo function of the candidate miRNA.
Results The expression of miR-127-3p decreased in kidney tissues from lupus nephritis patients and pristane induced lupus mice. miR-127-3p was found negatively regulating the type 1 IFN signalling by directly targeting JAK1 and knocking down of miR-127-3p enhanced type 1 IFN signalling. Overexpression of miR-127-3p prevented pristane induced lung haemorrhage.
Conclusions Our study shows miR-127-3p can inhibit IFN signalling and is reduced in kidneys of lupus nephritis patients indicating a new mechanism of overactivated IFN response in the kidney of SLE. In vivo inhibitory effects of miR-127-3p on IFN signalling suggest its therapeutic potential of treating lupus. Ongoing mouse model studies about the effects of miR-127-3p on lupus nephritis will give us more insights into its therapeutic value.
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