Circadian variation in the release of small extracellular vesicles can be normalized by vesicle number or TSG101

American Journal of Physiology. Renal Physiology
Erik H KoritzinskyPeter S T Yuen

Abstract

Numerous candidate biomarkers in urine extracellular vesicles (EVs) have been described for kidney diseases, but none are yet in clinical use, possibly due to a lack of proper normalization. Proper normalization corrects for normal biological variation in urine flow rate or concentration, which can vary by over one order of magnitude. Here, we observed inter- and intra-animal variation in urine excretion rates of small EVs (<200 nm in diameter) in healthy rats as a series of six 4-h fractions. To visualize intra-animal variation, we normalized a small EV excretion rate to a peak excretion rate, revealing a circadian pattern for each rat. This circadian pattern was distinct from urine volume, urine albumin, urine creatinine, and urine albumin-to-creatinine ratio. Furthermore, urine small EV excretion was not significantly altered by sex, food/water deprivation, or ischemic acute kidney injury. Urine excretion of the exosomal/small EV marker protein tumor susceptibility gene 101 (TSG101) displayed a similar circadian pattern to urine small EV excretion; both measurements were highly correlated (R2 = 0.85), with an average stoichiometry of 10.0 molecules of TSG101/vesicle in healthy rats. The observed stoichiometry of TSG101/vesic...Continue Reading

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Citations

Aug 28, 2020·Disease Markers·Christos MasaoutisStamatios Theocharis
Jun 21, 2020·International Journal of Molecular Sciences·Ahmed AbdeenMasahiro Ikeda
Dec 20, 2019·Therapeutic Advances in Respiratory Disease·Abdelnaby KhalyfaDavid Gozal
Jul 2, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Jing NingHequn Zou
Dec 12, 2020·Journal of Extracellular Vesicles·Fabian BraunRoman-Ulrich Müller
Apr 3, 2021·Advanced Drug Delivery Reviews·Sander A A KooijmansRaymond M Schiffelers
May 27, 2021·Critical Reviews in Toxicology·Brian N ChorleyAlison H Harrill
May 27, 2021·Journal of Extracellular Vesicles·Uta ErdbrüggerElena S Martens-Uzunova
Sep 25, 2021·Biomédica : revista del Instituto Nacional de Salud·Susana Novoa-Herrán

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Methods Mentioned

BETA
urine collections
urine collection
ELISA
fluorescence imaging
affinity purification
ELISAs

Software Mentioned

Odyssey
GraphPad
NTA
GraphPad Prism

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