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  • Title: RNAi Silencing of HIF-1α Ameliorates Lupus Development in MRL/lpr Mice.
    Author: Zhao W, Wu C, Li LJ, Fan YG, Pan HF, Tao JH, Leng RX, Ye DQ.
    Journal: Inflammation; 2018 Oct; 41(5):1717-1730. PubMed ID: 30043119.
    Abstract:
    Th17 cell and IL-17-mediated autoimmunity and inflammatory responses have been implicated in the development of organ damage in systemic lupus erythematosus (SLE), and new evidence suggests that hypoxia-inducible factor 1α (HIF-1α) enhances Th17 differentiation and promotes IL-17 production. However, the role of HIF-1α in the pathogenesis of lupus has not been examined. In this study, we silenced HIF-1α in vivo in a murine model of SLE to investigate whether lupus progression and the associated inflammatory pathways were affected by downregulating HIF-1α. Treatment with HIF1α-shRNA suppressed serum IL-17 level in MRL/lpr mice. Decreased anti-nucleosome antibody level, reduced urinary protein concentrations, ameliorated pathological damage, and remarkably reduced renal IgG and C3 depositions were observed in HIF1α-shRNA-treated group compared to those in the controls. Our results provide the first evidence for a role of HIF-1α in the pathogenesis of lupus and suggest a potential new therapeutic avenue for the treatment of lupus patients through reducing the HIF-1α level.
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