GLCCI1 is a novel component associated with the PI3K signaling pathway in podocyte foot processes

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. Research into the regulation of a kidney protein has provided insight into the pathways involved in diabetic kidney disease. The protein, called GCCLI1, is expressed in kidney cells called podocytes, which can be injured in diabetes. Chan-Wha Kim and colleagues from Korea University, Seoul, aimed to determine how GCCLI1 is regulated and what it does. They built on previous findings that other podocyte proteins are regulated by the PI3K pathway, a signaling pathway essential to many cellular processes and a possible target for treatment of diabetic kidney disease. In cultured cells and rat kidneys, GCCLI1 was expressed in the same locations as the podocyte proteins nephrin and synaptopodin, and was also regulated by the PI3K pathway. Nephrin and synaptopodin are essential for podocyte function, and the identical regulation of GCCLI1 suggests that it is similarly crucial.