| Author |
Shan, Shan Li, Jiangxia Liu, Qiji Liu, Zhaojian Ma, Xiaochun Gong, Yaoqin Yuan, Qianqian Bian, Xianli Liu, Na Gao, Fei Dang, Jie Qian, Yanyan Xin, Qian Yuan, Jupeng Liu, Guangyi |
| Description |
Author Affiliation: Xin Q ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Li J ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Dang J ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Bian X ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Shan S ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Yuan J ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Qian Y ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Liu Z ( Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong 250012, China); Liu G ( Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.); Yuan Q ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Liu N ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Ma X ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Gao F ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Gong Y ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China); Liu Q ( Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, China) |
| Abstract |
MicroRNA-155 (miR-155) was previously found involved in the development of systemic lupus erythematosus (SLE) and other autoimmune diseases and the inflammatory response; however, the detailed mechanism of miR-155 in SLE is not fully understood. To explore the in vivo role of miR-155 in the pathogenesis of SLE, miR-155-deficient Fas(lpr/lpr) (miR-155(-/-)Fas(lpr/lpr)) mice were obtained by crossing miR-155(-/-) and Fas(lpr/lpr) mice. Clinical SLE features such as glomerulonephritis, autoantibody levels, and immune system cell populations were compared between miR-155(-/-)Fas(lpr/lpr) and Fas(lpr/lpr) mice. Microarray analysis, RT-PCR, Western blot, and luciferase reporter gene assay were used to identify the target gene of miR-155. miR-155(-/-)Fas(lpr/lpr) mice showed milder SLE clinical features than did Fas(lpr/lpr)mice. As compared with Fas(lpr/lpr) mice, miR-155(-/-)Fas(lpr/lpr) mice showed less deposition of total IgA, IgM, and IgG and less infiltration of inflammatory cells in the kidney. Moreover, the serum levels of IL-4 and IL-17a, secreted by Th2 and Th17 cells, were lower in miR-155(-/-)Fas(lpr/lpr) than Fas(lpr/lpr) mice; the CD4(+)/CD8(+) T cell ratio was restored in miR-155(-/-)Fas(lpr/lpr) mice as well. Sphingosine-1-phosphate receptor 1 (S1PR1) was found as a new target gene of miR-155 by in vitro and in vivo studies; its expression was decreased in SLE patients and Fas(lpr/lpr) mice. miR-155(-/-)Fas(lpr/lpr) mice are resistant to the development of SLE by the regulation of the target gene S1pr1. miR-155 might be a new target for therapeutic intervention in SLE. |
