1. Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/TNFAIP3/NF-κB pathway
- Author
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Xiufen Ma, Yuhua Su, Yajing Liu, Chunxiao Guan, Chao Ma, and Shan Meng
- Subjects
0301 basic medicine ,Fibroblast-like synoviocyte ,lcsh:Diseases of the musculoskeletal system ,animal structures ,HAND2-AS1 ,Exosomes ,TNFAIP3 ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Western blot ,lcsh:Orthopedic surgery ,microRNA ,Basic Helix-Loop-Helix Transcription Factors ,Medicine ,Humans ,Orthopedics and Sports Medicine ,Rheumatoid arthritis ,Cells, Cultured ,Tumor Necrosis Factor alpha-Induced Protein 3 ,medicine.diagnostic_test ,business.industry ,Mesenchymal stem cell ,NF-kappa B ,miR-143-3p ,Mesenchymal Stem Cells ,Fibroblasts ,Synoviocytes ,Microvesicles ,lcsh:RD701-811 ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,embryonic structures ,Cancer research ,Surgery ,Tumor necrosis factor alpha ,RNA, Long Noncoding ,lcsh:RC925-935 ,business ,Research Article - Abstract
Background Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) was found to be elevated in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLSs). However, whether HAND2-AS1 functions as an exosomal lncRNA related to mesenchymal stem cells (MSCs) in RA progression is unknown. Methods The expression of HAND2-AS1, microRNA (miR)-143-3p, and tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) was detected using quantitative real-time polymerase chain reaction and Western blot. Cell proliferation, apoptosis, migration, and invasion were detected using cell counting kit-8, flow cytometry, and wound healing and transwell assays. The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL)-6 were analyzed using enzyme-linked immunosorbent assay. The level of phosphorylated-p65 was examined by Western blot. The binding interaction between miR-143-3p and HAND2-AS1 or TNFAIP3 was confirmed by the dual-luciferase reporter and RIP assays. Exosomes were isolated by ultracentrifugation and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Results HAND2-AS1 was lowly expressed in RA synovial tissues, and HAND2-AS1 re-expression suppressed the proliferation, motility, and inflammation and triggered the apoptosis in RA-FLSs via the inactivation of NF-κB pathway. Mechanistically, HAND2-AS1 directly sponged miR-143-3p and positively regulated TNFAIP3 expression, the target of miR-143-3p. Moreover, the effects of HAND2-AS1 on RA-FLSs were partially attenuated by miR-143-3p upregulation or TNFAIP3 knockdown. HAND2-AS1 could be packaged into hMSC-derived exosomes and absorbed by RA-FLSs, and human MSC-derived exosomal HAND2-AS1 also repressed above malignant biological behavior of RA-FLSs. Conclusion MSC-derived exosomes participated in the intercellular transfer of HAND2-AS1 and suppressed the activation of RA-FLSs via miR-143-3p/TNFAIP3/NF-κB pathway, which provided a novel insight into the pathogenesis and treatment of RA.
- Published
- 2020