POS0788 CIRCULATING EXOSOMES PROMOTE LUPUS NEPHRITIS IN MRL-LPR MICE

Abstract

Background:Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease that characterized by the loss of self-tolerance and the production of autoantibodies (autoAbs) [1, 2]. Lupus nephritis (LN), the severe organ-threatening manifestations of SLE, could cause massive damage to patients[3, 4]. Currently, some exosomal microRNAs (miRNAs) are considered as potential biomarkers in SLE. However, the role of exosomal miRNAs in Lupus Nephritis (LN) remains unclear.Objectives:The purpose of this study was to investigate molecular mechanism of plasma exosomal miRNAs in the development of Lupus Nephritis.Methods:Circulating exosomes were isolated from plasma of patients with LN, SLE without LN (NLN). Plasma exosomes were authenticated by Western Blot, Nanosight Tracking Analysis (NTA) and transmission electron microscopy (TEM). Fluorescence microscopy of co-cultured plasma exosomes and podocytes demonstrated that exosomes were uptaken into podocytes. Moreover, cell apoptosis and the inflammation factors was assessed using Western Blot. We analyzed the expression profiles of miRNAs in LN and NLN exosomes and the expression profiles of mRNAs of podocytes stimulated with LN and NLN exosomes with the help of next generation sequencing (NGS).Results:We demonstrate that exosomes derived from LN plasma could be taken by neighboring podocytes and promote the apoptosis of podocytes and the expression of inflammation factors. In addition, the sequencing found that miRNAs were differentially expressed in LN and NLN exosomes and mRNAs were differentially expressed in podocytes stimulated with LN and NLN exosomes.Conclusion:LN plasma exosomes have a potency to stimulate the apoptosis of podocytes and the expression of inflammation factors. Moreover, differentially expressed miRNAs in exosomes play a potential role in the development of LN.