Podocyte alpha-actinin induction precedes foot process effacement in experimental nephrotic syndrome.
Podocyte alpha-actinin induction precedes foot process effacement in experimental nephrotic syndrome.
复制标题
DOI：
10.1152/ajprenal.1997.273.1.f150
复制
发表时间：
1997-07
期刊：
影响因子：
--
通讯作者：
W. Smoyer;P. Mundel;Avneesh Gupta;M. J. Welsh
中科院分区：
文献类型：
--
作者：
W. Smoyer;P. Mundel;Avneesh Gupta;M. J. Welsh
足细胞与肾小球基底膜的附着被认为主要由α3/β1-整联蛋白和细胞骨架蛋白（包括肌动蛋白、talin、纽蛋白和α-肌动蛋白）介导。我们分析了用嘌呤霉素氨基核苷 (PAN) 诱导足细胞足突消失和肾病综合征过程中几个时间点大鼠肾小球中这些分子的表达。 PAN 注射导致肾小球 α-肌动蛋白显着诱导（与配对对照相比增加 40%，P < 0.01），这明显先于足细胞足突消失和蛋白尿的发生，并且几乎完全局限于足细胞。还观察到足突消失后肾小球 α 3 整合素的延迟诱导（与配对对照相比增加 44%，P < 0.01），但不限于足细胞。在疾病发展过程中的任何时间点，肾小球纽蛋白、talin、β1-整合素或总肌动蛋白表达均未发生显着变化。我们得出的结论是，在实验性肾病综合征中，足细胞中的α-辅肌动蛋白的诱导发生在足突消失之前。足细胞中这种肌动蛋白交联蛋白的表达改变可能在肾病综合征的足突消失中具有致病作用。
Attachment of podocytes to the glomerular basement membrane is thought to be mediated primarily by alpha 3/beta 1-integrins and by cytoskeletal proteins including actin, talin, vinculin, and alpha-actinin. We analyzed the expression of those molecules in rat glomeruli at several time points during induction of podocyte foot process effacement and nephrotic syndrome with puromycin aminonucleoside (PAN). PAN injection resulted in marked induction of glomerular alpha-actinin (40% increase vs. paired controls, P < 0.01), which clearly preceded development of podocyte foot process effacement and proteinuria and localized almost exclusively to podocytes. Delayed induction of glomerular alpha 3-integrin (44% increase vs. paired controls, P < 0.01) following foot process effacement was also observed but was not restricted to podocytes. No significant changes in glomerular vinculin, talin, beta 1-integrin, or total actin expression occurred at any time point during disease development. We conclude that foot process effacement is preceded by induction of alpha-actinin in podocytes in experimental nephrotic syndrome. Altered expression of this actin cross-linking protein in podocytes may have a pathogenic role in foot process effacement in nephrotic syndrome.