Shiga toxin (Stx) plays a central role in the etiology of hemolytic uremic syndrome (HUS) associated with Stx-producing Escherichia coli infection. The deposition of Stx2 in the renal collecting duct epithelial cells of rats administered Stx2 intravenously has been demonstrated by immunohistochemistry, and these rats were shown to develop substantial morphological changes in the kidney tubules, associated with polyuria. Severe polyuria was observed as an early event with no other obvious sequelae after Stx administration, in parallel with elevated urinary level of aquaporin 2 (AQP2) water channel protein that was determined by a sandwich EIA assay. Immunoblotting revealed that Stx treatment markedly induced an elevation in urinary AQP2 level and reduction in AQP2 protein in the renal plasma membranes. Elevated urinary AQP2 level was a more sensitive marker to assess Stx-induced renal tubular damage than urinary beta2-microglobulin or N-acetyl-beta-D-glucosaminidase in rats. Stx2 caused more severe renal tubular impairment than Stx1. Change in urinary AQP2 level by Stx1 and Stx2 at non-lethal doses of 40 ng/kg and 10 ng/kg, respectively, was reversed at 7 days in association with recovery of urinary concentrating ability, suggesting that there is a causative link.
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http://dx.doi.org/10.1016/s0024-3205(02)01618-1 | DOI Listing |
J Therm Biol
December 2024
NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, GA, 30602, USA. Electronic address:
Sci Rep
November 2024
TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan.
Exp Cell Res
January 2025
Department of Medical BioSciences, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:
Tubuloids are advanced in vitro models obtained from adult human or mouse kidney cells with great potential for modelling kidney function in health and disease. Here, we developed a polarized human and mouse tubuloid epithelium on cell culture inserts, namely Transwell™ filters, as a model of the distal nephron with an accessible apical and basolateral side that allow for characterization of epithelial properties such as leak-tightness and epithelial resistance. Tubuloids formed a leak-tight and confluent epithelium on Transwells™ and the human tubuloids were differentiated towards the distal part of the nephron.
View Article and Find Full Text PDFVet Clin Pathol
October 2024
Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Urinary extracellular vesicles (UEVs) are membranous particles that carry renal tubular transporter proteins. Here, we evaluate whether selected renal tubular transporter proteins can be detected in UEVs isolated from small volume (1-5 mL) canine urine samples of healthy dogs and canine patients with elevated circulating parathyroid hormone (PTH)/PTH-related peptide (PTHrp) concentrations, hypercortisolism, and primary hypoadrenocorticism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total creatinine content of each urine sample was calculated from urine volume and creatinine concentration.
View Article and Find Full Text PDFJCI Insight
November 2024
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Urinary concentration is an energy-dependent process that minimizes body water loss by increasing aquaporin 2 (AQP2) expression in collecting duct (CD) principal cells. To investigate the role of mitochondrial (mt) ATP production in renal water clearance, we disrupted mt electron transport in CD cells by targeting ubiquinone (Q) binding protein QPC (UQCRQ), a subunit of mt complex III essential for oxidative phosphorylation. QPC-deficient mice produced less concentrated urine than controls, both at baseline and after type 2 vasopressin receptor stimulation with desmopressin.
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