Loss of ezrin expression reduced the susceptibility to the glomerular injury in mice.
Loss of ezrin expression reduced the susceptibility to the glomerular injury in mice.
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DOI：
10.1038/s41598-018-22846-0
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发表时间：
2018-03-14
影响因子：
4.6
通讯作者：
Asano S
中科院分区：
文献类型：
--
作者：
Hatano R;Takeda A;Abe Y;Kawaguchi K;Kazama I;Matsubara M;Asano S
Ezrin在肾小球足细胞中高度表达，据报道，Ezrin与支架蛋白Na+/H+交换调节因子2 （NHERF2）和足alyxin（一种主要的唾液蛋白）形成多蛋白复合物。足足alyxin基因敲除小鼠在出生24小时内死亡，无尿性肾衰竭，而nherf2基因敲除小鼠肾小球功能无明显变化。然而，ezrin在肾小球足细胞中的生理作用尚不清楚。在这里，我们利用ezrin敲低小鼠（Vil2kd/kd）研究了ezrin在调节肾小球足细胞功能中的重要性。Vil2kd/kd小鼠未表现出明显的肾小球功能障碍、形态缺陷或足细胞中足alyxin和NHERF2的异常定位。因此，我们研究了ezrin缺陷对Rho-GTPase活性的影响，因为ezrin与Rho-GTPase解离抑制剂（Rho-GDI）相互作用，后者在足细胞肌动蛋白组织的调节中起关键作用。在Vil2kd/kd肾小球中，与野生型（WT）肾小球相比，基线时Rac1活性显著降低。此外，Vil2kd/kd小鼠对肾小球损伤的易感性降低。在WT肾小球中，Rac1活性在肾病条件下增强，但在Vil2kd/kd肾小球中保持在基线水平，这表明ezrin的缺失通过抑制Rac1激活来保护足细胞免受损伤诱导的形态学改变。
Ezrin is highly expressed in glomerular podocytes and is reported to form a multi-protein complex with scaffold protein Na+/H+ exchanger regulatory factor 2 (NHERF2) and podocalyxin, a major sialoprotein. Podocalyxin-knockout mice died within 24 h of birth with anuric renal failure, whereas NHERF2-knockout mice show no apparent changes in the glomerular functions. However, the physiological roles of ezrin in glomerular podocytes remain unclear. Here, we investigated the importance of ezrin in the regulation of glomerular podocyte function using ezrin-knockdown mice (Vil2kd/kd). The Vil2kd/kd mice did not exhibit apparent glomerular dysfunction, morphological defects or abnormal localisation of podocalyxin and NHERF2 in podocytes. Thus, we investigated the influence of ezrin defects on Rho-GTPase activity, as ezrin interacts with the Rho-GTPase dissociation inhibitor (Rho-GDI), which plays a key role in the regulation of podocyte actin organisation. In Vil2kd/kd glomeruli, Rac1 activity was significantly reduced compared to wildtype (WT) glomeruli at baseline. Furthermore, Vil2kd/kd mice showed reduced susceptibility to glomerular injury. In WT glomeruli, Rac1 activity was enhanced in nephrotic conditions, but remained at baseline levels in Vil2kd/kd glomeruli, suggesting that loss of ezrin protects podocytes from injury-induced morphological changes by suppressing Rac1 activation.
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影响因子：
7.8
作者：
Raucher, D;Sheetz, M P
通讯作者：
Sheetz, M P
DOI：
10.1084/jem.194.1.13
发表时间：
2001-07-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Doyonnas R;Kershaw DB;Duhme C;Merkens H;Chelliah S;Graf T;McNagny KM
通讯作者：
McNagny KM
影响因子：
3.9
作者：
Viswanatha R;Bretscher A;Garbett D
通讯作者：
Garbett D
影响因子：
19.6
作者：
Hugo, C;Nangaku, M;Johnson, RJ
通讯作者：
Johnson, RJ
DOI：
10.1083/jcb.200410083
发表时间：
2005-04-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tamura A;Kikuchi S;Hata M;Katsuno T;Matsui T;Hayashi H;Suzuki Y;Noda T;Tsukita S;Tsukita S
通讯作者：
Tsukita S