miR‐34a in extracellular vesicles from bone marrow mesenchymal stem cells reduces rheumatoid arthritis inflammation via the cyclin I/ATM/ATR/p53 axis
| Autor: | Xuedong Wang, Wenjun Huang, Bing Luo, Wei Cheng, Xike Zhou, Juan Gu, Wu Huaiguo, Yueping Wang, Xinjia Hu |
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| Rok vydání: | 2021 |
| Předmět: |
rheumatoid arthritis
Male 0301 basic medicine Biopsy Apoptosis Inflammation Arthritis Rheumatoid Extracellular Vesicles 03 medical and health sciences Cyclin I 0302 clinical medicine In vivo medicine Animals Cells Cultured ATM/ATR/p53 signalling pathway Cyclin Chemistry Mesenchymal stem cell MicroRNA‐34a Mesenchymal Stem Cells Original Articles Cell Biology Synoviocytes Hedgehog signaling pathway Rats MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation inflammation MicroRNA 34a 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article Bone marrow Tumor Suppressor Protein p53 medicine.symptom Biomarkers Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | Extracellular vesicles (Evs) participate in the development of rheumatoid arthritis (RA), but the mechanisms remain unclear. This study aimed to determine the mechanism by which microRNA‐34a (miR‐34a) contained in bone marrow mesenchymal stem cell (BM‐MSC)‐derived Evs functions in RA fibroblast‐like synoviocytes (RA‐FLSs). BM‐MSC‐derived Evs and an Evs inhibitor were extracted. A rat model of RA was established. miR‐34a gain‐ and loss‐of‐function experiments were performed, and the inflammation in rat synovial fluid and tissues was detected. The role of miR‐34a in RA‐FLSs was also measured in vitro. The target gene of miR‐34a was predicted using the online software TargetScan and identified using a dual‐luciferase reporter gene assay, and the activation of the ATM/ATR/p53 signalling pathway was assessed. BM‐MSC‐derived Evs mainly elevated miR‐34a expression, which reduced RA inflammation in vivo and inhibited RA‐FLS proliferation and resistance to apoptosis in vitro, while inhibited miR‐34a expression enhanced RA development. In addition, miR‐34a could target cyclin I to activate the ATM/ATR/p53 signalling pathway, thus inhibiting abnormal RA‐FLS growth and RA inflammation. Our study showed that miR‐34a contained in BM‐MSC‐derived Evs could reduce RA inflammation by inhibiting the cyclin I/ATM/ATR/p53 signalling pathway. |
| Databáze: | OpenAIRE |
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