Deshan Li, Yinhang Yu, Yu Zhang and Guiping Ren
Northeast Agricultural University, China
Posters-Accepted Abstracts: J Diabetes Metab
FGF21 has been widely accepted as a regulator for glucose and lipid metabolism. A recent report indicated that circulating FGF21 levels are elevated in the serum and synovial fluid of patients with Rheumatoid Arthritis (RA), but the role of FGF21 in the development of RA is totally unknown. The aim of this study is to investigate efficacy of FGF21for treatment of RA and the molecular mechanisms underline the therapeutic effect on collagen-induced arthritis (CIA). Mice with CIA were subcutaneously administered with FGF21 (5, 2 or 1 mg·kg-1·d-1), IL-1β antibody (5 mg·kg-1·d-1), IL-17A antibody (5 mg·kg-1·d-1) and dexamethasone (DEX) (1 mg·kg- 1·d-1), respectively. The effects of treatment were determined by arthritisseverity score, histological damage and cytokine production. The activation of NF-κB was analyzed by Western blotting. We also detected the levels of oxidative stress parameters. Our results showed that FGF21 had beneficial effects on clinical symptom and histological lesion of CIA mice. Similar to antibody and DEX, FGF21 treatment alleviated the severity of arthritis by reducing humoral and cellular immune responses and down-regulating the expression of pro-inflammatory cytokines. FGF21 treatment also reduced the expression of TNF-α, IL-1β, IL-6, IFN-γ and MMP-3 and increased level of IL-10 in the spleen tissue or the plasma of CIA mice in a dose-dependent manner. Furthermore, FGF21 inhibited IκBα degradation and NF-κB p65 nuclear translocation and induced significant changes of oxidative stress parameters (MDA, SOD, CAT, GSH-PX and GSH) in the plasma. We therefore conclude that FGF21 exerts the therapeutic efficacy for RA through antioxidant reaction and inhibiting NF-κB inflammatory pathway. This study provides evidence that FGF21 may be a promising therapeutic agent for RA patients.
Email: deshanli@163.com
