FGF23 facilitates IL-1β synthesis in rheumatoid arthritis through activating PI3K, Akt, and NF-κB pathways

Sung-Lin Hu; Louis Anoop Thadevoos; Trung-Loc Ho; Yen-You Lin; Hsien-Te Chen; Chien-Chung Huang; Chen-Ming Su; Chih-Hsin Tang

doi:10.1002/tox.24180

FGF23 facilitates IL-1β synthesis in rheumatoid arthritis through activating PI3K, Akt, and NF-κB pathways

Environ Toxicol. 2024 Feb 21. doi: 10.1002/tox.24180. Online ahead of print.

Authors

Sung-Lin Hu^{1

2}, Louis Anoop Thadevoos³, Trung-Loc Ho³, Yen-You Lin⁴, Hsien-Te Chen^{5

6}, Chien-Chung Huang^{1

7}, Chen-Ming Su⁵, Chih-Hsin Tang^{1

3

4

8

9

10}

Affiliations

¹ School of Medicine, China Medical University, Taichung, Taiwan.
² Department of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu, Taiwan.
³ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁴ Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
⁵ Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan.
⁶ Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
⁷ Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
⁸ Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
⁹ Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan.
¹⁰ Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan.

PMID: 38380842
DOI: 10.1002/tox.24180

Abstract

Rheumatoid arthritis (RA) is a well-known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by osteocytes and osteoblasts, involves an essential effect in pathogenesis of RA. IL-1β is a vital proinflammatory factor in the development of RA. However, the role of FGF23 on IL-1β synthesis in RA has not been fully explored. Our analysis of database revealed higher levels of FGF23 and IL-1β in RA samples compared with healthy controls. High-throughput screening demonstrated that IL-1β is a potential candidate factor after FGF23 treatment in RA synovial fibroblasts (RASFs). FGF23 concentration dependently promotes IL-1β synthesis in RASFs. FGF23 enhances IL-1β expression by activating the PI3K, Akt, and NF-κB pathways. Our findings support the notion that FGF23 is a promising target in the remedy of RA.

Keywords: FGF23; IL-1β; NF-κB; rheumatoid arthritis; synovial fibroblasts.

Abstract

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