A vital role for Angptl3 in the PAN-induced podocyte loss by affecting detachment and apoptosis in vitro.
A vital role for Angptl3 in the PAN-induced podocyte loss by affecting detachment and apoptosis in vitro.
复制标题
Angptl3 通过影响体外分离和细胞凋亡，在 PAN 诱导的足细胞损失中发挥重要作用。
DOI：
10.1186/s12882-015-0034-4
复制
发表时间：
2015-03-29
期刊：
影响因子：
2.3
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Dai R;Lin Y;Liu H;Rao J;Zhai Y;Zha X;Fang X;Xu H
足细胞脱落和凋亡是导致足细胞丢失的两个危险因素，f -肌动蛋白重排参与了脱落和凋亡。然而，促进足细胞脱离和凋亡的事件的性质以及脱离是否与细胞凋亡同时发生尚不清楚。此前，研究发现血管生成素样3 （Angptl3）可诱导足细胞中f -肌动蛋白重排。在本研究中，我们研究了Angptl3是否影响足细胞的丢失（脱离和凋亡）以及Angptl3影响足细胞丢失的确切过程。在条件永生化小鼠足细胞中，利用重组小鼠Angptl3蛋白（rm-Angptl3）模拟Angptl3过表达模型，转染小干扰RNA （siRNA）敲低Angptl3的表达。采用流式细胞术和末端脱氧核苷酸转移酶介导的dUTP镍端标记法检测细胞凋亡。使用共聚焦显微镜评估f -肌动蛋白重排。Western blot法检测Angptl3、整合素α3β1、整合素连接激酶（integrin-linked kinase， ILK）、p53、caspase 3和整合素β1磷酸化水平。在嘌呤霉素氨基核苷（PAN）诱导的足细胞损伤模型中，rm-Angptl3加速足细胞的丢失，发生脱离和凋亡，并参与了f -肌动蛋白重排。然而，通过siRNA敲低Angptl3可显著改善这些损伤。观察到的效果与整合素α3β1、ILK和p53的改变部分相关，而与caspase 3无关。Angptl3是一个新的因子，通过影响离体和细胞凋亡参与pan诱导的足细胞丢失。本研究有助于加深对足细胞丢失机制的理解，并为开发低表达Angptl3成功治疗足细胞损伤的新方法奠定基础。
Podocyte detachment and apoptosis are two risk factors causing podocyte loss, F-actin rearrangement is involved in detachment and apoptosis. However, the nature of events that promote detachment and apoptosis of podocytes and whether detachment occurred simultaneously with apoptosis are still unclear. Previously, it was found that angiopoietin-like3 (Angptl3) induces F-actin rearrangement in podocytes. In this study we investigate whether Angptl3 influences podocyte loss (detachment and apoptosis) and the process through which Angptl3 exactly influenced the podocyte loss. In conditionally immortalized mice podocytes, recombinant mice Angptl3 protein (rm-Angptl3) was used to mimic Angptl3 overexpression model and transfection with small interfering RNA (siRNA) to knockdown the expression of Angptl3. Both flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were used to detect apoptosis. Rearrangement of F-actin was assessed using confocal microscopy. Western blot assay was used to measure levels of Angptl3, integrin α3β1, integrin-linked kinase (ILK), p53, caspase 3, and phosphorylation of integrin β1. In a puromycin aminonucleoside (PAN)-induced podocyte injury model, rm-Angptl3 accelerated the loss of podocytes, both detachment and apoptosis occurred, and F-actin rearrangement is involved in the process. However, knockdown of Angptl3 by siRNA markedly ameliorated these injuries. Observed effects were partially correlated with the altered integrin α3β1, ILK and p53, rather than caspase 3. Angptl3 is a novel factor involved in the PAN-induced podocyte loss by affecting detachment and apoptosis in vitro. This study helps to deepen the understanding of the mechanisms of podocyte loss and lays the foundation for developing a new successful therapy for podocyte injury via lower expression of Angptl3.
登录
查看更多内容
影响因子：
18.2
作者：
Greka A;Mundel P
通讯作者：
Mundel P
生存素在嘌呤霉素氨基核苷诱导的足细胞损伤中的作用。
影响因子：
5.6
作者：
Li X;Zhang X;Li X;Ding F;Ding J
通讯作者：
Ding J
血管生成素样 3 的表达与嘌呤霉素诱导的足细胞损伤相关
影响因子：
--
作者：
Rao Jia;Xu Hong;Hao Chuanming
通讯作者：
Hao Chuanming
影响因子：
4.8
作者：
Kretzler, M;Teixeira, VPC;Holthöfer, H
通讯作者：
Holthöfer, H
血管生成素样蛋白 3 通过改变体外去氧肾上腺素表达来调节足细胞的运动性和通透性
DOI：
10.1016/j.bbrc.2010.07.027
发表时间：
2010-08-13
影响因子：
3.1
作者：
Gao, Xia;Xu, Hong;Zha, Xiliang
通讯作者：
Zha, Xiliang