Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis.
增加的自噬对抗体和干扰素-α 诱导的狼疮性肾炎足细胞损伤具有细胞保护作用。

摘要

OBJECTIVE:More recent studies suggested that defects in autophagy contribute to the pathogenesis of SLE, especially in adaptive immunity. 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 an establishment on the role of autophagy in pathogenesis of LN and as a therapy target.
METHODS:Systemic and organ-specific aetiologies of autophagy were first evaluated by autophagy protein quantification in tissue homogenates in MRL 
                        lpr/lpr
                     lupus prone and female C57BL mice. Analysis of gene expression was also adopted in human blood and urine sediments. Then, some key mediators of the disease, including complement inactivated serum, IgG from patients with LN (IgG-LN) and interferon (IFN)-α were chosen to induce podocyte autophagy. Podocyte injuries including apoptosis, podocin derangement, albumin filtration and wound healing were monitored simultaneously with autophagy steady-state and flux.
RESULTS:Elevated LC3B in kidney homogenates and increased autophagosomes in podocyte from MRL 
                        lpr/lpr
                     were observed. In humans, mRNA levels of some key autophagy genes were increased in blood and urinary sediments, and podocyte autophagosomes were observed in renal biopsies from patients with LN. Complement inactivated serum, IgG-LN and IFN-α could induce podocyte autophagy in a time-dependent and dosage-dependent manner, and by reactive oxygen species production and mTORC1 inhibition, respectively. Autophagy inhibition aggravated podocyte damage whereas its inducer relieved the injury.
CONCLUSION:Podocyte autophagy is activated in lupus-prone mice and patients with lupus nephritis. Increased autophagy is cytoprotective against antibody and interferon-α induced podocyte injury.

译文

目的: 最近的研究表明,自噬缺陷参与了 SLE 的发病机制,尤其是适应性免疫。狼疮性肾炎 (LN) 的发生和发展是肾脏常驻细胞调节免疫反应和病理过程之间复杂相互作用的最终结果, 但是关于自噬在 LN 发病机制中的作用以及作为治疗靶点的建立,仍然有许多缺失的信息。
方法: 自噬的系统性和器官特异性病因首先通过 MRL 中组织匀浆中的自噬蛋白定量进行评估。
Lpr/lpr
易患狼疮的雌性 C57BL 小鼠。人类血液和尿液沉积物中也采用了基因表达分析。然后,选择疾病的一些关键介质,包括补体灭活血清、 LN 患者的 IgG (IgG-LN) 和干扰素 (IFN)-α 来诱导足细胞自噬。足细胞损伤包括细胞凋亡、 podocin 紊乱、白蛋白滤过和伤口愈合同时监测自噬稳态和流量。
结果: 肾脏匀浆中 LC3B 升高,足细胞自噬体从 MRL 中增加
Lpr/lpr
观察到。在人类中,一些关键自噬基因的 mRNA 水平在血液和尿液沉积物中增加,在 LN 患者的肾活检中观察到足细胞自噬体。补体灭活血清、 IgG-LN 和 IFN-α 可诱导足细胞自噬,呈时间依赖性和剂量依赖性,并分别通过活性氧产生和 mTORC1 抑制。自噬抑制加重足细胞损伤,而其诱导剂减轻损伤。
结论: 狼疮性肾炎易感小鼠和狼疮性肾炎患者足细胞自噬被激活。增加的自噬对抗体和干扰素-α 诱导的足细胞损伤具有细胞保护作用。

podocyte

肾内泌尿 细胞 基础研究专业名词
概述  :  

足细胞即肾小球脏层上皮细胞,因其在基底膜侧的胞质呈“伪足”样突起而得名,是结构复杂的终末分化细胞。足细胞与足细胞下间隙、肾小球基底膜、内皮细胞及内皮细胞窗孔、内皮细胞表面膜共同构成肾小球滤过屏障。上述结构相互独立又密不可分,足细胞参与肾小球基底膜重构,维系内皮细胞功能及肾小球毛细血管袢结构。足细胞对维系肾小球滤过屏障尤为重要,足细胞损伤是肾小球性蛋白尿发生的主要机制,与多种肾小球疾病的发生发展关系密切。 结构基础与功能 1.结构基础:

podocyte   /pɔdə'sait/

释    义   n. 足状突细胞

例    句   Mitochondrial oxidative stress in renal cortex is markedly associated with the effacement and broadened of foot process,reduced podocyte number and nephrin expression.肾皮质线粒体氧化应激与足突消失和扩大、足细胞数量减少和肾组织表达有关。

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