Pro-angiogenic effect of exosomal microRNA-103a in mice with rheumatoid arthritis via the downregulation of hepatocyte nuclear factor 4 alpha and activation of the JAK/STAT3 signaling pathway

M Chen, MH Li, N Zhang, WW Sun, H Wang, YA Wang, Y Zhao, W Wei

Article ID: 3958
Vol 35, Issue 2, 2021
DOI: https://doi.org/10.23812/20-537-A
Received: 9 May 2021; Accepted: 9 May 2021; Available online: 9 May 2021; Issue release: 9 May 2021

Abstract

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial membrane, accompanied by hyperplasia and neo-angiogenesis, which promote local inflammation. Macrophage-derived exosomes have been reported to enhance inflammation and the immune response. In the present study, we identified a novel exosomal microRNA (miR)-103a, which aids in the regulation of inflammation and angiogenesis in mice with RA, and attempted to identify the underlying mechanism. Initially, a mouse model of RA was established. Thereafter, exosomes were isolated from macrophage RAW264.7 cells and evaluated through transmission electron microscopy and nanoparticle tracking analysis. After prediction and verification of the target genes of miR-103a, RT-qPCR was used to assess miR-103a and HNF4A expression in mice with RA. High expression of miR-103a and low expression of HNF4A were observed in mice with RA, thus, miR-103a was found to target and downregulate HNF4A. Exosomal miR-103a promoted inflammation and angiogenesis in mice with RA which was accompanied by an increase in the levels of factors associated with inflammation and angiogenesis. However, an opposite trend was observed upon HNF4A elevation. Exosomal miR-103a was also found to activate the JAK/STAT3 signaling pathway. In conclusion, exosomal miR-103a inhibited the expression of HNF4A to activate the JAK/STAT3 signaling pathway, thereby exacerbating RA in mice.


Keywords

Janus kinase/signal mammalian;MicroRNA;angiogenesis;hepatocyte nuclear factor 4 alpha;inflammation;rheumatoid arthritis;transducers and activators of transcription 3


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