Identification of novel rheumatoid arthritis-associated MiRNA-204-5p from plasma exosomes.

Autor: Wu LF; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 215123, Suzhou, Jiangsu, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 215123, Suzhou, Jiangsu, China., Zhang Q; Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Mo XB; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 215123, Suzhou, Jiangsu, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 215123, Suzhou, Jiangsu, China., Lin J; Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Wu YL; Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Lu X; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 215123, Suzhou, Jiangsu, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 215123, Suzhou, Jiangsu, China., He P; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 215123, Suzhou, Jiangsu, China.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 215123, Suzhou, Jiangsu, China., Wu J; Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Guo YF; Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Wang MJ; Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Ren WY; Cam-Su Genomic Resource Center, Medical College of Soochow University, 215123, Suzhou, Jiangsu, China., Deng HW; Center of Bioinformatics and Genomics, Department of Global Biostatistics and Data Science, Tulane University, New Orleans, LA, USA., Lei SF; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 215123, Suzhou, Jiangsu, China. leisf@suda.edu.cn.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 215123, Suzhou, Jiangsu, China. leisf@suda.edu.cn., Deng FY; Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University, 215123, Suzhou, Jiangsu, China. fdeng@suda.edu.cn.; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, 215123, Suzhou, Jiangsu, China. fdeng@suda.edu.cn.
Jazyk: angličtina
Zdroj: Experimental & molecular medicine [Exp Mol Med] 2022 Mar; Vol. 54 (3), pp. 334-345. Date of Electronic Publication: 2022 Mar 30.
DOI: 10.1038/s12276-022-00751-x
Abstrakt: Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.
(© 2022. The Author(s).)
Databáze: MEDLINE