a Renal Division, Peking University First Hospital,Peking University Institute of Nephrology,Key Laboratory of Renal Disease , Ministry of Health of China , Beijing , People's Republic of China.
b Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University) , Ministry of Education , Beijing , People's Republic of China.
Autophagy. 2019 May;15(5):908-912. doi: 10.1080/15548627.2019.1580512. Epub 2019 Feb 17.
Recent studies suggest that defects in macroautophagy/autophagy contribute to the pathogenesis of systemic lupus erythamatosus (SLE), especially in adaptive immunity. The occurrence and progression of lupus nephritis (LN) is the end result of complex interactions between regulation of immune responses and pathological process by renal resident cells, but there is still a lot of missing information for establishing the role of autophagy in the pathogenesis of LN, and as a therapy target. In our recent study, we observed that autophagy is activated in LN, especially in podocytes. Based on in vitro assays, many of the most important mediators of the disease - patients' sera, patients' IgG and IFNA/IFN-α - can induce autophagy in both murine and human podocytes, by reactive oxygen species production or MTORC1 inhibition; autophagy activation negatively associates with podocyte injury. With regard to intervention, autophagy activators can protect against podocyte injury, whereas autophagy inhibitors aggravate injury. Taken together, our findings suggest that podocyte autophagy is involved in lupus renal protection and may be a therapeutic target. These data shed new light on the role of rapamycin and autophagy inducers in the treatment of SLE. Abbreviations: ALB: albumin; ARHGDIB: Rho GDP dissociation inhibitor beta; APOL1: apolipoprotein L1; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG16L2: autophagy related 16 like 2; BECN1: beclin 1; CDKN1B: cyclin dependent kinase inhibitor 1B; CLEC16A, C-type lectin domain containing 16A; CYBB: cytochrome b-245 beta chain; DC: dendritic cell; DRAM1: DNA damage regulated autophagy modulator 1; eQTL: expression quantitative trait loci; GWAS: genome-wide association study; IFNA: interferon alpha; IRGM: immunity related GTPase M; LRRK2: leucine rich repeat kinase 2; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MTMR3: myotubularin related protein 3; LAP" LC3-associated phagocytosis; LN: lupus nephritis; NOD: non-obese diabetic; NPHS2: NPHS2, podocin; PBMC: peripheral blood mononuclear cell; RUBCN: rubicon autophagy regulator; SLE: systemic lupus erythematosus.
最近的研究表明，巨自噬/自噬缺陷导致全身性红斑狼疮（SLE）的发病机制，特别是在适应性免疫中。狼疮肾炎（LN）的发生和进展是免疫反应调节和肾固有细胞病理过程之间复杂相互作用的最终结果，但仍有大量信息缺失，无法确定自噬在 LN 发病机制中的作用，以及作为治疗靶点。在我们最近的研究中，我们观察到 LN 中自噬被激活，特别是在足细胞中。基于体外实验，疾病的许多最重要的介质——患者的血清、患者的 IgG 和 IFNA/IFN-α——可以通过活性氧产生或 MTORC1 抑制，诱导鼠和人足细胞中的自噬；自噬的激活与足细胞损伤呈负相关。关于干预，自噬激活剂可以保护足细胞免受损伤，而自噬抑制剂则加重损伤。总的来说，我们的发现表明，足细胞自噬参与狼疮肾保护，可能是一个治疗靶点。这些数据为雷帕霉素和自噬诱导剂在治疗 SLE 中的作用提供了新的见解。缩写词：ALB：白蛋白；ARHGDIB：Rho GDP 解离抑制剂β；APOL1：载脂蛋白 L1；ATG5：自噬相关 5；ATG7：自噬相关 7；ATG16L2：自噬相关 16 样 2；BECN1：自噬相关蛋白 1；CDKN1B：细胞周期蛋白依赖性激酶抑制剂 1B；CLEC16A，C 型凝集素结构域包含 16A；CYBB：细胞色素 b-245β链；DC：树突状细胞；DRAM1：DNA 损伤调节自噬调节剂 1；eQTL：表达数量性状基因座；GWAS：全基因组关联研究；IFNA：干扰素α；IRGM：免疫相关 GTP 酶 M；LRRK2：富含亮氨酸重复激酶 2；MAP1LC3B：微管相关蛋白 1 轻链 3β；MTMR3：肌管素相关蛋白 3；LAP" LC3 相关吞噬作用；LN：狼疮肾炎；NOD：非肥胖糖尿病；NPHS2：NPHS2，足细胞；PBMC：外周血单核细胞；RUBCN：Rubicon 自噬调节剂；SLE：全身性红斑狼疮。
