Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0106621
Title: The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1
Authors: Itoh M.
Nakadate K.
Horibata Y.
Matsusaka T.
Xu J.
Hunziker W. 
Sugimoto H.
Keywords: albumin
protein ZO1
membrane protein
protein ZO1
TJP1 protein, human
animal cell
animal experiment
animal model
animal tissue
Article
blood filtration
controlled study
female
gene deletion
glomerular dysfunction
glomerular filtration barrier
glomerulosclerosis
immaturity
male
molecular pathology
morphogenesis
mouse
nonhuman
podocyte filtration slit
protein expression
proteinuria
regulatory mechanism
Tjp1 gene
animal
biosynthesis
endothelium cell
gene expression regulation
genetics
glomerulus
glomerulus basement membrane
human
kidney circulation
knockout mouse
metabolism
pathology
podocyte
Animals
Endothelial Cells
Gene Expression Regulation
Glomerular Basement Membrane
Humans
Kidney Glomerulus
Membrane Proteins
Mice
Mice, Knockout
Podocytes
Renal Circulation
Zonula Occludens-1 Protein
Issue Date: 2014
Citation: Itoh M., Nakadate K., Horibata Y., Matsusaka T., Xu J., Hunziker W., Sugimoto H. (2014). The structural and functional organization of the podocyte filtration slits is regulated by Tjp1/ZO-1. PLoS ONE 9 (9) : e106621. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0106621
Rights: Attribution 4.0 International
Abstract: 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. © 2014 Itoh et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161777
ISSN: 19326203
DOI: 10.1371/journal.pone.0106621
Rights: Attribution 4.0 International
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