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EPO promotes the progression of rheumatoid arthritis by inducing desialylation via increasing the expression of neuraminidase 3.
- Source :
-
Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Apr 11; Vol. 83 (5), pp. 564-575. Date of Electronic Publication: 2024 Apr 11. - Publication Year :
- 2024
-
Abstract
- Objective: Erythropoietin (EPO) known as an erythrocyte-stimulating factor is increased in patients with rheumatoid arthritis (RA). Nevertheless, the function of EPO in the process of RA and relative mechanism needs to be further clarified.<br />Methods: The level of EPO in serum and synovial fluid from patients with RA and healthy controls was determined by . Collagen-induced arthritis (CIA) mice were constructed to confirm the role of EPO on RA pathogenesis. Differentially expressed genes (DEGs) of EPO-treated fibroblast-like synoviocyte (FLS) were screened by transcriptome sequencing. The transcription factor of neuraminidase 3 (NEU3) of DEGs was verified by double luciferase reporting experiment, DNA pulldown, electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative PCR (qPCR) assay.<br />Results: The overexpression of EPO was confirmed in patients with RA, which was positively associated with Disease Activity Score 28-joint count. Additionally, EPO intervention could significantly aggravate the joint destruction in CIA models. The upregulation of NEU3 was screened and verified by transcriptome sequencing and qPCR in EPO-treated FLS, and signal transducer and activator of transcription 5 was screened and verified to be the specific transcription factor of NEU3. EPO upregulates NEU3 expression via activating the Janus kinase 2 (JAK2)-STAT5 signalling pathway through its receptor EPOR, thereby to promote the desialylation through enhancing the migration and invasion ability of FLS, which is verified by JAK2 inhibitor and NEU3 inhibitor.<br />Conclusion: EPO, as a proinflammatory factor, accelerates the process of RA through transcriptional upregulation of the expression of NEU3 by JAK2/STAT5 pathway.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Animals
Humans
Mice
Cell Proliferation
Cells, Cultured
Fibroblasts metabolism
STAT5 Transcription Factor metabolism
Synovial Membrane metabolism
Arthritis, Experimental genetics
Arthritis, Experimental metabolism
Arthritis, Rheumatoid genetics
Arthritis, Rheumatoid metabolism
Erythropoietin metabolism
Neuraminidase metabolism
Synoviocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1468-2060
- Volume :
- 83
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Annals of the rheumatic diseases
- Publication Type :
- Academic Journal
- Accession number :
- 38272667
- Full Text :
- https://doi.org/10.1136/ard-2023-224852