AB0210 THE GLOBAL EXPRESSION OF MIRNAS AND LNCRNAS IN THE EXOSOMES OF SYSTEMIC SCLEROSIS PLASMA AND NEUTROPHIL AND RELATED FUNCTIONS
Authors: LI Liya, Zuo Xiaoxia, DI Liu, Luo Hui, Zhu Honglin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is a systemic autoimmune disease with unknown pathogenesis. Exosomes (EXOs) are cell-derived vesicles 30-150 nm in size that contain various mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and proteins. Plasma EXOs play wide roles in various diseased, however, little is known in SSc. <h3>Objectives</h3> Investigate the global expression of miRNAs and lncRNAs in the EXOs of SSc plasma and neutrophil. Explore the potential function of EXOs in the pathogenesis of SSc. <h3>Methods</h3> EXOs were respectively isolated from plasma, cultured neutrophil supernatants, and were identified by transmission electron microscopy. Global expression of miRNAs and lncRNAs form 5 SSc and 5 normal controls was analysis by IlluminaHiSeq 3000 platform. Differentiated expressed and bioinformatics analysis was performed by edgeR, limma package, GO, KEGG, and cytoscape. Furthermore, we used the EXOs stimulated human dermal microvascular endothelial cells (HDMECs) and human primary skin fibroblasts, and explore the potential functions of EXOs. <h3>Results</h3> 1. In plasma EXOs, we identified a total of 37 miRNAs and 479 lncRNAs that showed significant differences between the two groups. Among them, 26 of upregulated miRNAs were involved in the ErbB signalling pathway; 11 of downregulated miRNAs were involved in the MAPK signalling pathway, TGF-β signalling pathway, AMPK signalling pathway;299 of upregulated lncRNAs were involved in the PI3K-Akt signalling pathway, p53 signalling pathway;180 of downregulated lncRNAs were involved in lysosome. 2. In neutrophil EXOs, we identified a total of 22 miRNAs and 281 lncRNAs that showed significant differences between the two groups. Among them, 12 of upregulated miRNAs were involved in the Wnt signalling pathway; 10 of downregulated miRNAs were involved in the MAPK signalling pathway, AMPK signalling pathway; 119 of upregulated lncRNAs were involved in interleukin-23 signalling pathway;162 of downregulated lncRNAs were involved in the signalling by GPCR, signalling by NOTCH and TRAIL. 3. After stimulated with SSc plasma EXOs, the expression levels of has-miR-324-5p and SP1/SMAD2, has-miR-624-5p and PIK3RCB, has-miR-483-5p and MAPK1 were negatively correlated, the expression levels of ENST00000562409.1 and OSMR, ENST00000601511.1 and HMGB1/NRAS were positively correlated, variably in HDMECs and human primary skin fibroblasts. 4. After stimulated with SSc neutrophil EXOs, the expression levels of has-miR-1268a and PRKCA, has-miR-299-3p and IGF1R were negatively correlated, the expression levels of ENST00000520562.1 and IL23R, ENST00000596567.1 and TFDP2, ENST00000608572.1 and HDAC2 were positively correlated, variably in neutrophil, HDMECs and human primary skin fibroblasts. 5. These miRNAs and lncRNAs with consistent expression might be involved in the pathogenesis of SSc EXOs. <h3>Conclusion</h3> Our study identified and confirmed differentially miRNAs and lncRNAs in the neutrophil EXOs and plasma EXOs. Those genes may be involved in the pathological mechanism of SSc, such as has-miR-324-5p and SP1/SMAD2, has-miR-624-5p and PIK3RCB, has-miR-483-5p and MAPK1, ENST00000520562.1 and IL23R, ENST00000596567.1 and TFDP2, ENST00000608572.1 and HDAC2. <h3>Acknowledgement</h3> This study was funded by grants from the National Key Research and Development Program of China (2016YFC0903900), National Natural Science Foundation of China (81671622), Hunan Provincial Natural Science Foundation (2018JJ3823), Clinical Research Fund of Xiangya Hospital Central South University (2014L10) and Independent Innovation Projects of Central South University (2018zzst290). <h3>Disclosure of Interests</h3> None declared