Podocyte Injury Caused by Indoxyl Sulfate, a Uremic Toxin and Aryl-Hydrocarbon Receptor Ligand

• DOI: 10.1371/journal.pone.0108448
• Publication Date: 2014-09-22T18:04:50Z
• Authors: Osamu Ichii; Saori Otsuka-Kana...; Teppei Nakamura; Masaaki Ueno; Yasuhiro Kon; Weiping Chen; Avi Z. Rosenberg; Jeffrey B. Kopp
• Keywords: 0301 basic medicine; 0303 health sciences; Podocytes; Science; Q; 491; R; Kidney; Ligands; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Receptors, Aryl Hydrocarbon; Medicine; Animals; Indican; Research Article

Indoxyl sulfate is a uremic toxin and ligand of the aryl-hydrocarbon receptor (AhR), transcriptional regulator. Elevated serum indoxyl levels may contribute to progressive kidney disease associated vascular disease. We asked whether injures podocytes in vivo vitro. Mice exposed for 8 w exhibited prominent tubulointerstitial lesions with damage. sulfate-exposed mice microalbuminuria showed ischemic changes, while more severely affected increased mesangial matrix, segmental solidification, mesangiolysis. In normal mouse kidneys, AhR was predominantly localized podocyte nuclei. 2 h, isolated glomeruli manifested Cyp1a1 expression, indicating activation. After sulfate, foot process effacement, cytoplasmic vacuoles, focal granular wrinkled pattern podocin synaptopodin expression. Furthermore, vimentin expression glomerulus compared controls. Glomerular characteristic mRNAs decreased, including Actn4, Cd2ap, Myh9, Nphs1, Nphs2, Podxl, Synpo, Wt1. vitro, immortalized-mouse nuclear translocation beginning 30 min after 1 mM exposure, there phospho-Rac1/Cdc42 at h. exposure 24 pro-inflammatory phenotype, perturbed actin cytoskeleton, decreased podocyte-specific genes, cell viability. immortalized human podocytes, treatment caused injury, mRNA proteins, as well integrins, collagens, cytoskeletal bone morphogenetic cytokine chemokine propose that basal activity regulate function under conditions, activation by contributes glomerular injury.