The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1.
The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1.
复制标题
DOI：
10.1371/journal.pone.0106621
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sugimoto H
中科院分区：
文献类型：
--
作者：
Itoh M;Nakadate K;Horibata Y;Matsusaka T;Xu J;Hunziker W;Sugimoto H
肾小球的血液滤过对于生理内环境平衡是必不可少的。肾小球的滤器由三个不同的部分组成：有窗口的内皮细胞、肾小球基底膜和构成裂隙隔膜的足细胞的交错的足突。最近的研究表明，足细胞在血液滤过以及蛋白尿和肾小球硬化的发病机制中起着至关重要的作用；然而，足细胞滤过屏障的分子机制尚不完全清楚。在本研究中，我们认为由Tjp1基因编码的紧密连接蛋白1(Tjp1或ZO-1)在建立足细胞滤过屏障中起重要作用。足细胞特异性缺失Tjp1下调足细胞膜蛋白的表达，损害足突的交错和裂隙横隔膜的形成，导致肾小球功能障碍。我们发现，在肾小球形态发生的最后阶段，足细胞过滤屏障可能需要两个独立单位的整合，即先前存在的上皮连接成分和新合成的足细胞特异性成分，其中Tjp1是不可或缺的。结合以往在人和动物模型中发现Tjp1在肾小球疾病中表达降低的结果，我们的结果表明Tjp1的抑制可以直接加重肾小球疾病，突出了Tjp1作为一个潜在的治疗靶点。
Blood filtration in the kidney glomerulus is essential for physiological homeostasis. The filtration apparatus of the kidney glomerulus is composed of three distinct components: the fenestrated endothelial cells, the glomerular basement membrane, and interdigitating foot processes of podocytes that form the slit diaphragm. Recent studies have demonstrated that podocytes play a crucial role in blood filtration and in the pathogenesis of proteinuria and glomerular sclerosis; however, the molecular mechanisms that organize the podocyte filtration barrier are not fully understood. In this study, we suggest that tight junction protein 1 (Tjp1 or ZO-1), which is encoded by Tjp1 gene, plays an essential role in establishing the podocyte filtration barrier. The podocyte-specific deletion of Tjp1 down-regulated the expression of podocyte membrane proteins, impaired the interdigitation of the foot processes and the formation of the slit diaphragm, resulting in glomerular dysfunction. We found the possibility that podocyte filtration barrier requires the integration of two independent units, the pre-existing epithelial junction components and the newly synthesized podocyte-specific components, at the final stage in glomerular morphogenesis, for which Tjp1 is indispensable. Together with previous findings that Tjp1 expression was decreased in glomerular diseases in human and animal models, our results indicate that the suppression of Tjp1 could directly aggravate glomerular disorders, highlights Tjp1 as a potential therapeutic target.
登录
查看更多内容
P-钙粘蛋白缺陷型小鼠的早熟乳腺发育。
DOI：
10.1083/jcb.139.4.1025
发表时间：
1997-11-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Radice GL;Ferreira-Cornwell MC;Robinson SD;Rayburn H;Chodosh LA;Takeichi M;Hynes RO
通讯作者：
Hynes RO
影响因子：
6
作者：
Li, Yingjian;Kang, Young Sun;Liu, Youhua
通讯作者：
Liu, Youhua
影响因子：
3.3
作者：
Katsuno, Tatsuya;Umeda, Kazuaki;Tsukita, Sachiko
通讯作者：
Tsukita, Sachiko
影响因子：
15.9
作者：
Kos, CH;Le, TC;Pollak, MR
通讯作者：
Pollak, MR
影响因子：
30.8
作者：
Boute, N;Gribouval, O;Antignac, C
通讯作者：
Antignac, C