Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis
Authors' conclusion
The FGF pathway is a critical signaling pathway in relapse RA.
Study context
- Population
- Patients with rheumatoid arthritis (RA) in relapse and in remission (matched synovial tissue samples); rat collagen-induced arthritis (CIA) modelsix matched synovial tissue samples
- Participants
- 3 vs 3
- Comparison
- Synovial FLSs in relapse RA vs remission
- Relapse RAn = 3
- Remissionn = 3reference
Methodological detailsSingle-cell RNA sequencing (scRNA-seq), spatial transcriptomics, qPCR and multiplex immunohistochemistry (mIHC) validation, in vitro and in vivo (rat CIA model)
- scRNA-seq
- Spatial transcriptomics
- qPCR and mIHC validation
- In vitro and in vivo (rat CIA model)
Main finding
As reported in the abstract
- Lining and sublining FLS subsets identified by scRNA-seq
- Fibroblast growth factor (FGF) pathway highly activated in lining FLSs from relapse RA; mIHC confirmed increased FGF10 expression
- Type I interferon pathway also activated in lining FLSs, but independent of the FGF10 pathway in vitro
- FGF10 knockdown by siRNA in FLSs significantly reduced RANKL expression
- Recombinant FGF10 enhanced bone erosion in primary human pannus cell culture; FGFR1 inhibitor attenuated it
- FGFR1 inhibitor had a therapeutic effect in CIA rat model
Original publication
Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis. Arthritis Rheumatol. Published 28 November 2023. doi:10. 1002/ art. 42674
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