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- W3135899644 abstract "Abstract Rationale : Lupus nephritis (LN) is a major risk factor for morbidity and mortality in systemic lupus erythematosus patients, and lupus nephritis treatment is limited to immunosuppressive therapy with many problems. Vitamin D receptor (VDR) can regulate NLRP3 inflammasome which plays critical roles in LN pathogenesis. Objectives : This study was designed to explore the therapeutic effect of VDR agonist on LN and its potential mechanisms, aiming to elucidatethe optimal therapy for LN. Findings : In vivo, treatment of MRL/lpr mice since 8 weeks of age with VDR agonist paricalcitol for 8 weeks decreased disease pathogenesis of LN with markedly improved renal pathological changes, decreased urine protein and serum anti-ds-DNA antibody level in a time-depended manner. In MRL/lpr mice of 16 weeks of age with LN, the expression of NLRP3/caspase-1/IL-1β/IL-18 axis was upregulated detecteded by ELISA, RT-PCR, western blot and immunohistochemistry, while when treated with VDR agonist paricalcitol, expression of this axis was decreased significantly. Further, it is proved that VDR agonist paricalcitol modulated NLRP3/caspase-1/IL-1β/IL-18 axis via inhibiting NF-κB, in addition, co-immunoprecipitation results showed that VDR agonist suppressed NF-κB nuclear translocation by competitively binding with importin 4. In vitro, anti-dsDNA antibody induced apoptosis and upregulation of NF-κB/NLRP3/caspase-1/IL-1β/IL-18 axis in mRTECs, which could be reversed by VDR agonist paricalcitol. Conclusions : Vitamin D receptor agonist may be a promising novel therapeutic strategy for patients with lupus nephritis, which paves the way for future preclinical/clinical studies." @default.
- W3135899644 created "2021-03-15" @default.
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- W3135899644 date "2020-09-10" @default.
- W3135899644 modified "2023-10-16" @default.
- W3135899644 title "VDR inhibits NLRP3 signal in lupus nephritis by competitively binding with importin 4 to suppress NF-κB nuclear translocation" @default.
- W3135899644 doi "https://doi.org/10.21203/rs.3.rs-73578/v1" @default.
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