Abstract
Background: 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, we investigated Its protective effects and underlying mechanism in MRL/lpr mice, a well-studied animal model for lupus.Methods: At the age of 11 weeks, forty-eight MRL/lpr mice were randomly divided into two groups with 24 mice per group: the VitD3-treated group and control group. Mice in the VitD3-treated group received 4μg/kg 1,25-dihydroxyvitamin D3 in 1% dimethyl sulfoxide (DMSO) intraperitoneal injection twice a week for 3 weeks (mice were executed at 0,2,4,6 weeks after treatment); mice in the control group treated with intraperitoneal injection of 1% DMSO for 3 weeks (mice were executed at 0,2,4,6 weeks after injections). The mice were sacrificed and the serum and kidney samples were collected respectively at planned intervals. Then the skin lesions, histological changes, inflammatory factors (TNF-α, IL-17) and immunological markers (A-ds DNA, C3, IgG, IgM) with time were analyzed between the groups. Furthermore, the NF-κB and MAPKs signaling pathways were also detected to explicate the underlying mechanism. Results: 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.Conclusion: This study shows that 1,25-dihydroxyvitamin D3 exerts a protective effect against lupus nephritis via 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 with time was revealed.