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Uromodulin and the study of urinary extracellular vesicles.
J Extracell Biol
November 2024
Division of Nephrology, Department of Medicine University of Virginia Charlottesville Virginia USA.
Urinary extracellular vesicles (uEVs) are a promising substrate for discovering new biomarkers. In order to investigate the origin of uEVs and the cargo they carry, some types of downstream analysis of uEVs may require concentration and enrichment as well as removal of contaminating substances. Co-isolation of the abundant urinary protein uromodulin with uEVs can be a problem, and may interfere with some techniques, in particular with proteomic analysis tools.
View Article and Find Full Text PDFUrinary Extracellular Vesicles: Ultracentrifugation Method.
Methods Mol Biol
April 2021
Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Recently, urinary extracellular vesicles (EVs) have garnered interest as a potential source of noninvasive biomarkers of diseases related to urinary organs (kidney, bladder, urethra, and prostate).Ultracentrifugation is considered the gold standard method for isolation of EVs. However, the precipitates after ultracentrifugation steps are usually contaminated with soluble proteins, such as the Tamm-Horsfall protein (uromodulin).
View Article and Find Full Text PDFCirculating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel.
Sci Transl Med
October 2019
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
High serum concentrations of kidney-derived protein uromodulin [Tamm-Horsfall protein (THP)] have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the kidney and systemically. Consistent with this experimental data, the concentration of circulating THP in patients with surgery-induced acute kidney injury (AKI) correlated with systemic oxidative damage.
View Article and Find Full Text PDFA novel role for Tamm-Horsfall protein (uromodulin) in the renal tubule.
Kidney Int
October 2018
Department of Anatomy, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address:
Tamm-Horsfall protein (THP)/uromodulin, the most abundant urinary protein, is produced in the thick ascending limb of the loop of Henle. Besides immunological functions, it has regulatory impact on ion transport and volume regulation. It had been debated whether the distal convoluted tubule is a source for THP as well.
View Article and Find Full Text PDFTamm-Horsfall protein/uromodulin deficiency elicits tubular compensatory responses leading to hypertension and hyperuricemia.
Am J Physiol Renal Physiol
June 2018
Department of Urology, New York University School of Medicine, New York, New York.
Expression of Tamm-Horsfall protein (THP or uromodulin) is highly restricted to the kidney thick ascending limb (TAL) of loop of Henle. Despite the unique location and recent association of THP gene mutations with hereditary uromodulin-associated kidney disease and THP single nucleotide polymorphisms with chronic kidney disease and hypertension, the physiological function(s) of THP and its pathological involvement remain incompletely understood. By studying age-dependent changes of THP knockout (KO) mice, we show here that young KO mice had significant salt and water wasting but were partially responsive to furosemide, due to decreased luminal translocation of Na-K-Cl cotransporter 2 (NKCC2) in the TAL.
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