Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis.
Increased autophagy is cytoprotective against podocyte injury induced by antibody and interferon-α in lupus nephritis.
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自噬增加对狼疮性肾炎中抗体和干扰素-α 诱导的足细胞损伤具有细胞保护作用。
DOI：
10.1136/annrheumdis-2018-213028
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发表时间：
2018-12
影响因子：
27.4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Qi YY;Zhou XJ;Cheng FJ;Hou P;Ren YL;Wang SX;Zhao MH;Yang L;Martinez J;Zhang H
最近的研究表明，自噬缺陷有助于SLE的发病机制，特别是在获得性免疫中。狼疮性肾炎（lupus nephritis，LN）的发生和发展是免疫调节和病理过程相互作用的结果，但自噬在LN发病机制中的作用及其作为治疗靶点的研究仍有很多缺失。首先通过MRLlpr/lpr狼疮易感小鼠和雌性C57 BL小鼠组织匀浆中的自噬蛋白定量来评估自噬的全身和器官特异性病因。同时对人血和尿沉渣进行基因表达分析。然后选择疾病的关键介质，包括补体灭活血清、LN患者IgG（IgG-LN）和IFN-α诱导足细胞自噬。足细胞损伤，包括细胞凋亡，podocin紊乱，白蛋白过滤，伤口愈合的同时监测自噬稳态和流量。观察到肾匀浆中LC 3B升高和来自MRLlpr/lpr的足细胞中自噬体增加。在人类中，血液和尿沉淀物中一些关键自噬基因的mRNA水平增加，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均能诱导足细胞自噬，并呈时间和剂量依赖性，分别通过活性氧和mTORC 1抑制诱导足细胞自噬。自噬抑制加重足细胞损伤，而自噬诱导剂减轻足细胞损伤。足细胞自噬在狼疮易感小鼠和狼疮肾炎患者中被激活。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。
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. Systemic and organ specific etiologies of autophagy were firstly evaluated by autophagy protein quantification in tissue homogenates in MRLlpr/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 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. Elevated LC3B in kidney homogenates and increased autophagosomes in podocyte from MRLlpr/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 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. 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.
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非规范自噬抑制自身炎症，类似狼疮的对垂死细胞的反应。
影响因子：
64.8
作者：
Martinez J;Cunha LD;Park S;Yang M;Lu Q;Orchard R;Li QZ;Yan M;Janke L;Guy C;Linkermann A;Virgin HW;Green DR
通讯作者：
Green DR
DOI：
10.1016/j.clim.2016.09.012
发表时间：
2017-12
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
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通讯作者：
Niewold TB
影响因子：
6
作者：
Migliorini, Adriana;Angelotti, Maria L.;Anders, Hans-Joachim
通讯作者：
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自噬通过保护高血糖诱导的荚膜细胞损伤，减轻糖尿病肾小球损伤。
影响因子：
3.7
作者：
Fang L;Zhou Y;Cao H;Wen P;Jiang L;He W;Dai C;Yang J
通讯作者：
Yang J
影响因子：
20.3
作者：
Bride, Karen L.;Vincent, Tiffaney;Teachey, David T.
通讯作者：
Teachey, David T.