Urinary
excretion pattern of exosomal aquaporin-2 in rats that received gentamicin.
Am J Physiol Renal Physiol 307: F1227–F1237, 2014. First published
October 22, 2014; doi:10.1152/ajprenal.00140.2014.—Urinary exosomes
are nano-sized vesicles secreted into urine from all types of renal
epithelial cells and are known to contain possible biomarker proteins
for renal diseases. Gentamicin has been reported to decrease the level
of renal aquaporin (AQP)2, which is known to be mainly expressed in
renal collecting ducts and excreted into the urine via exosomes. In the
present study, we investigated whether urinary exosomal AQP2 could
serve as a potential biomarker for gentamicin-induced nephrotoxicity,
especially collecting duct cell dysfunction. Gentamicin was given to
rats intraperitoneally once every day starting on day 0. Gentamicin
significantly increased the plasma creatinine concentration from day 5
and beyond. Also, gentamicin induced polyuria and a defective urine
concentration mechanism on day 7, suggesting gentamicin-induced
collecting duct cell dysfunction. Immunoblot analysis showed that
gentamicin significantly increased urinary exosomal AQP2 excretion
on day 1 but decreased it on day 7 compared with the control group.
Similarly, increased excretion of exosomal tumor susceptibility gene
101 protein, frequently used as an exosome marker protein, was
observed on day 1. However, gentamicin did not significantly affect
the urinary excretion of exosomal tumor susceptibility gene 101 on
day 7. Gentamicin slightly decreased renal AQP2 expression on day
2 and markedly decreased it on day 8. These data strongly suggest that
the use of urinary exosomal AQP2 as a biomarker may allow detection
of gentamicin-induced collecting duct cell dysfunction. Furthermore,
urinary exosomal AQP2 might also be useful for the early
detection of |
