GLCCI1 is a novel component associated with the PI3K signaling pathway in podocyte foot processes.
GLCCI1 is a novel component associated with the PI3K signaling pathway in podocyte foot processes.
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DOI：
10.1038/emm.2016.28
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发表时间：
2016-05-13
影响因子：
12.8
通讯作者：
Kim CW
中科院分区：
文献类型：
--
作者：
Kim SH;Kim HJ;Kim CW
足细胞足突相互交叉形成狭缝隔膜，对肾小球滤过屏障至关重要。糖皮质激素诱导的转录本1（GLCCI 1）是转录调控，但其在足细胞中的信号转导途径是未知的。本研究的主要目的是研究足细胞足突蛋白的调节，并研究GLCCI 1在磷酸肌醇3-激酶（PI 3 K）通路中的作用，使用高糖诱导的足细胞和链脲佐菌素诱导的糖尿病大鼠。在足细胞和大鼠肾脏，GLCCI 1被发现是高度特异性的肾小球和足细胞足的过程类似于其他足细胞特异性蛋白质（nephrin，podocin，synatopodin和podocalyxin）的基础上，逆转录-PCR，免疫印迹，免疫荧光和免疫电镜分析。此外，通过用PI 3 K抑制剂（渥曼青霉素）治疗，高血糖条件下GLCCI 1表达水平的降低得以恢复。免疫荧光分析证实，GLCCI 1共定位nephrin和synaptopodin在体内和体外。最后，链脲佐菌素诱导的糖尿病大鼠的免疫电镜数据表明，GLCCI 1也定位于足细胞足突。因此，GLCCI 1是足细胞足突的一个组成部分，其表达似乎是通过PI 3 K途径调节的。
Podocyte foot processes are interdigitated to form the slit diaphragm and are crucial for the glomerular filtration barrier. Glucocorticoid-induced transcript 1 (GLCCI1) is transcriptionally regulated, but its signaling pathway in podocytes is unknown. The main objective of this study was to investigate the regulation of podocyte foot process proteins and to investigate the role of GLCCI1 in the phosphoinositide 3-kinase (PI3K) pathway using high glucose-induced podocytes and streptozotocin-induced diabetic rats. In podocytes and rat kidneys, GLCCI1 was found to be highly specific for the glomerulus and podocyte foot processes similar to other podocyte-specific proteins (nephrin, podocin, synatopodin and podocalyxin) based on reverse transcription-PCR, western blotting, immunofluorescence and immunoelectron microscopy analyses. In addition, the decrease in the GLCCI1 expression level under hyperglycemic conditions was restored by treatment with a PI3K inhibitor (wortmannin). Immunofluorescence analysis confirmed that GLCCI1 colocalized with nephrin and synaptopodin both in vivo and in vitro. Finally, immunoelectron microscopy data from streptozotocin-induced diabetic rats showed that GLCCI1 also localized in podocyte foot processes. Hence, GLCCI1 is a component of podocyte foot processes, and its expression appears to be regulated via the PI3K pathway.