NOD2在狼疮性肾炎发病机制中的作用和潜在信号通路的研究

Systemic lupus erythematosus (SLE) is an autoimmune disease that seriously threatens the health of young women. Lupus nephritis (LN) is one of the common complications of SLE, which is also one of the key factors in determining the outcomes of lupus patients. The pathogenesis of LN is not completely clarified. Recently, studies have found that NOD2 expressed in resident renal cells, and the increased expression of NOD2 participated in renal ischemia-reperfusion injury and diabetic nephropathy damage. But the role of NOD2 in the pathogenesis of LN has not been reported yet. Our preliminary study has found that NOD2 expression is up-regulated in resident renal cells in LN patients. Thus, we expect to discover the pathogenic role of NOD2 in LN patients, by investigating the NOD2 expression and the activation of the downstream signaling pathways on cultured human resident renal cell lines under the LN inflammatory pathogenic conditions. Moreover, we want to establish NOD2-/- lupus mice model for evaluating the overall influence of NOD2 in the development of LN. Our study may confirm our proposed hypothesis “Increased expression of NOD2 on resident renal cells may involve in the renal injury of LN, and the mechanisms are probably related to the activation of the MAPK and NF-κB signaling pathways, and the release of downstream pro-inflammatory cytokines”. Our results may provide a new idea and target for the treatment of LN patients.

系统性红斑狼疮（SLE）是一种严重威胁育龄期女性健康的自身免疫性疾病，狼疮性肾炎（LN）是其常见的合并症，也是决定狼疮患者预后的关键因素之一，其发病机制尚未彻底阐明。最近的研究发现NOD2在肾脏固有细胞上表达，其表达的增多参与了肾缺血再灌注损伤及糖尿病肾病的损害。但是，目前尚无NOD2在LN方面的相关报道。我们的初步研究发现LN的肾脏固有细胞上存在NOD2表达上调，故本课题拟用体外培养的人肾脏固有细胞系，通过模拟LN致病炎性条件来研究NOD2在LN中的作用机制及其下游信号通路，并通过建立NOD2-/-狼疮小鼠模型，从整体水平揭示NOD2在LN的发生发展中的地位。本课题将证实我们提出的“肾脏固有细胞上NOD2表达的增多参与了LN肾脏损伤的发生，其作用机制可能与MAPK和NF-κB信号通路的激活和下游促炎因子的释放有关”这一假说，为LN的防治提供新思路和新靶点。