title: GLCCI1 is a novel component associated with the PI3K signaling pathway in podocyte foot processes.
abstract: 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.
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Chan-Wha
authors.initials: CW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D007678:Kidney Glomerulus / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: C000611569:GLCCI1 protein, rat; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011506:Proteins; C503969:Synpo protein, rat; C113267:nephrin; D019869:Phosphatidylinositol 3-Kinases