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.
J Biol Regul Homeost Agents
; 35(2): 629-640, 2021.
Article
in En
| MEDLINE
| ID: mdl-33887899
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Arthritis, Rheumatoid
/
MicroRNAs
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Biol Regul Homeost Agents
Journal subject:
BIOLOGIA
/
BIOQUIMICA
Year:
2021
Type:
Article