狼疮性肾炎（LN）是系统性红斑狼疮最为常见的合并症和死亡原因之一，致病机理的研究对LN诊断和治疗策略的制定有着重要的临床意义。我们前期研究发现补体C1q、Wnt/β-catenin和 白介素6(IL-6)信号都参与LN的临床病理发生过程。本项目将通过对下述内容的研究来探讨C1q介导的Wnt/β-catenin和IL-6信号交互作用在LN致病中的作用机制：(1) 检测 LN患者体液Wnt/β-catenin信号和IL-6含量，揭示它们在临床LN中的相关性；(2) 利用C1q和血清免疫沉淀复合物刺激肾小球细胞系和外周血单核细胞，体外分析C1q介导Wnt/β-catenin与IL-6信号交互作用；(3) 制备 IL-6基因缺陷狼疮小鼠肾炎模型体内探讨Wnt/β-catenin和IL-6信号交互作用在LN病理发生过程中的可能机制。本项目的完成将为临床LN的诊断标志和治疗靶标的深入研究提供理论依据。

Lupus nephritis (LN) is one of the most common complication and cause of death in patients with systemic lupus erythematosus (SLE), a better understanding of mechanisms of its pathogenesis is important for the diagnosis and regiment design for treatment of this disease in clinical settings. Our previous studies revealed the involvements of C1q complement, Wnt/β-catenin and interleukin-6 (IL-6) in the pathogenesis of LN, indicating a C1q-mediated interaction between Wnt/β-catenin and IL-) signaling in development of LN. This proposal thus aimed to explore the C1q-mediated cross-talk between Wnt/β-catenin and IL-6 signaling in the pathogenesis via an accomplishment of below three specific aims as following: (1) evaluating the concentration of proteins of Wnt/β-catenin and IL-6 signaling in renal tissues, sera and/or urines in SLE patients LN clinical, which will allow us to access a clinical relevance between these two signaling; (2) in vitro study to demonstrate the C1q-mediated cross-talk between Wnt/β-catenin and IL-6 signaling by stimulating glomerular cell lines and peripheral blood mononuclear cells (PBMCs) using immunoprecipitation complex isolated from human sera; (3) uncovering the pathogenic role and mechanism of cross-talk between Wnt/β-catenin and IL-6 by generating IL-6 gene deficient lupus nephritis of murine model to access pathological and dynamic changes of the expression of Wnt/β-catenin and IL-6 signaling molecules. An accomplishment of this study will lay a foundation for further investigations in identification of novel biomarkers and targets for the diagnosis and treatment of LN.