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

Circadian variation in the release of small extracellular vesicles can be normalized by vesicle number or TSG101. Am J Physiol Renal Physiol. 2019 Aug 07;: Authors: Koritzinsky EH, Street JM, Chari RR, Glispie DM, Bellomo TR, Aponte AM, Star RA, Yuen PST 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 an order of magnitude. Here, we observed inter- and intra-animal variation in urine excretion rates of small EVs (< 200 nm diameter) in healthy rats as a series of six 4-hour fractions. To visualize intra-animal variation, we normalized small EV excretion rate to 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. Further, 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 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 o...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research