1,25-dihydroxyvitamin D3 ameliorates lupus nephritis through inhibiting NF-κB and MAPKs signaling pathways in MRL/lpr mice

Abstract Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus(SLE).However,the etiology and pathogenesis of LN remain unknown. 1,25-dihydroxyvitamin D3(1,25-(OH)2-VitD3)is the active form of vitamin D, which has been known to have important functions in inflammation and immune diseases. In this study, its protective effects and underlying mechanism with time were investigated in MRL/lpr mice, a well-studied animal model for lupus. Briefly, MRL/lpr mice were randomly divided into VitD3-treated group and control group. Both groups were treated for 3 weeks. Then at four time points after treatment, the skin lesions, histological changes, inflammatory factors and immunological examinations with time were analyzed between the groups. Furthermore, the NF-κB and MAPKs signaling pathways with time were also detected to explicate the underlying mechanism. Compared to the control group, mice in the VitD3-treated group showed less skin lesions, less kidney injury, lower serum anti-ds DNA antibody, lower inflammatory cytokines TNF-α, IL-17 and higher serum complement C3; they also had less deposition of IgG, IgM and C3 within glomeruli. Moreover, the expressions of NF-κB and MAPKs signaling pathways were decreased, while those levels were increased with time. This study shows that 1,25-dihydroxyvitamin D3 exerts a protective effect against lupus nephritis via inhibiting pro-inflammatory cytokines and regulating the NF-κB and MAPKs signaling pathways, which will be developed as a potential agent for the treatment of lupus nephritis. And the relationship between lupus activity and NF-kB and MAPKs signaling pathways over time was revealed.