ATG5介导的自噬在狼疮性肾炎中的致病机制

Lpus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE) with high incidence and poor prognosis. Although LN has been studied for centuries, the pathogenesis remains unclear. As an important degradation pathway, autophagy is being recognized to plays a comprehensive role in immunity regulation. Our previous studies found that autophagy related 5(ATG5) was a pivotal susceptibility gene of SLE. Mice with podocyte-specific deletion of Atg5 were susceptible to glomerulopathy. The current project will focus on the pathogenic role of ATG5 mediated autophagy in LN. Plenty of data from human and mice and cell will provide scientific clues for disease etiology and pathology.

狼疮性肾炎（LN）是系统性红斑狼疮（SLE）最严重的并发症之一，其发病率高且预后不良。目前出现肾脏损伤的发病机制尚不清楚。自噬作为一种重要的机体清除和细胞存亡机制，参与多种免疫调节反应。在前期工作中，我们发现自噬基因ATG5无论常见变异还是少见变异，均与SLE发病易感性明显相关。特异性足细胞Atg5敲除的小鼠更容易发生肾小球肾炎。因此我们推测，ATG5介导的自噬参与LN致病。本课题中，我们采用人体实验、动物实验、细胞实验，利用遗传学、药物干预、分子生物学、免疫性、病理学等方法，从整体、靶器官、细胞及分子水平上，全面分析ATG5介导的自噬与狼疮性肾炎临床表型、靶器官损害的关系，并寻找可能的机制，为LN的治疗提供更多的线索。