Angiopoietin-like protein 3 regulates the motility and permeability of podocytes by altering nephrin expression in vitro
Angiopoietin-like protein 3 regulates the motility and permeability of podocytes by altering nephrin expression in vitro
复制标题
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
复制
发表时间：
2010-08-13
影响因子：
3.1
通讯作者：
Zha, Xiliang
中科院分区：
文献类型：
--
作者：
Gao, Xia;Xu, Hong;Zha, Xiliang
众所周知，足细胞损伤在大量蛋白尿中起着至关重要的作用。足细胞运动性的增加导致足细胞足突（FP）消失，这是足细胞损伤的典型形式。我们之前的研究表明，肾小球足细胞可以表达血管生成素样蛋白3（ANGFTL3），并且功能失调的肾小球中ANGPTL3的增加与足细胞FP消失相关。然而，人们对 ANGPTL3 在足细胞损伤中的作用知之甚少。在这项研究中，我们研究了 ANGPTL3 对足细胞运动性和通透性以及足细胞关键分子去氧肾上腺素表达的影响。通过刮伤和transwell迁移实验，我们发现ANGPTL3过表达显着增加了足细胞的运动性，而通过RNA干扰敲低ANGPTL3后，运动性仍与对照组相同。阿霉素（ADR）治疗显着促进足细胞运动。然而，敲除ANGPTL3后，相同剂量的ADR治疗不能促进运动。此外，我们还检测了 FITC-BSA 在足细胞单层中的扩散，以研究 ANGPTL3 是否可以通过增加足细胞运动性来促进蛋白质损失。结果表明，足细胞 FITC-BSA 通透性的变化与运动的变化相对应。此外，我们发现ANGPTL3过表达显着增加了去氧肾上腺素的表达，但当RNAi减弱ANGPTL3时，ADR诱导的去氧肾上腺素的上调被显着抑制。总之，我们发现ANGPTL3能够调节足细胞的运动性和通透性，并且ANGPTL3的调节机制可能与去氧肾上腺素表达的改变有关。 (C) 2010 Elsevier Inc. 保留所有权利。
It is well known that podocyte injury plays a vital role in massive proteinuria. The increase of podocyte motility results in podocyte foot process (FP) effacement, a typical form of podocyte injury. Our previous studies demonstrated that glomerular podocytes can express angiopoietin-like protein 3 (ANGFTL3) and that the increase of ANGPTL3 in dysfunctional glomerulus is correlated with podocyte FP effacement. Little is known, however, about the role of ANGPTL3 in podocyte injury. In this study, we investigated ANGPTL3's effect on the motility and permeability of podocytes and on the expression of nephrin, a key molecule in podocytes. By scrape-wound and transwell migration assay, we found that ANGPTL3 over-expression significantly increased podocyte motility, whereas after ANGPTL3 knockdown by RNA interference, motility remained the same as that of the control group. Adriamycin (ADR) treatment significantly promoted podocyte motility. However, the same dose of ADR treatment could not promote motility after the knockdown of ANGPTL3. In addition, we assayed the diffusion of FITC-BSA across the podocytes' monolayer to investigate whether ANGPTL3 could promote protein loss by means of an increase in podocyte motility. The results showed that the changes in the FITC-BSA permeability of the podocytes corresponded to changes in motility. Furthermore, we found that ANGPTL3 over-expression dramatically increased the expression of nephrin but that the up-regulation of nephrin induced by ADR was significantly inhibited when ANGPTL3 was diminished by RNAi. In conclusion, we found ANGPTL3 to be capable of regulating the motility and permeability of podocytes and that the mechanism of ANGPTL3's regulation could be associated with the altered expression of nephrin. (C) 2010 Elsevier Inc. All rights reserved.