Abstract
Aquaporin-1 (AQP1) and AQP2 are important proteins involved in the regulation of renal water handling. Both AQPs have been found in urinary extracellular vesicles (uEVs) (uEV-AQP1 and -AQP2). Cisplatin, an antineoplastic agent, is known to down-regulate renal AQP1 and AQP2. However, the effect of cisplatin on the release of uEV-AQP1 and -AQP2 is largely unknown. In this study, we examined whether treatment of rats with cisplatin affected the release of uEV-AQP1 and -AQP2. Blood tests indicated that renal function was little altered at 24 h after cisplatin treatment but thereafter decreased dramatically at all of the other time points examined. Release of uEV-AQP1 was slightly increased at 24 h and decreased at 168 h. On the other hand, release of uEV-AQP2 was decreased dramatically at 24 h, and the decrease was maintained during the experimental period. These data suggest that uEV-AQP2 can be used to detect early renal impairment due to cisplatin. Furthermore, a combination of uEV-AQP2 and -AQP1 may be useful for estimation of cisplatin-induced renal injury in a stage-dependent manner.
Highlights
Aquaporins (AQPs) are membrane water channels, and at least 13 aquaporin isoforms (AQP0 to12) have been identified in mammals
The summarized data for body weight, urine volume, plasma creatinine, and urea nitrogen concentrations are shown in Figure 1 and Table S2
Urine volume volume in the cisplatin group significantly decreased at 72 h and increased at 120 h in comparison in the cisplatin group significantly decreased at 72 h and increased at 120 h in comparison with with the control group
Summary
Aquaporins (AQPs) are membrane water channels, and at least 13 aquaporin isoforms Seven AQPs (AQP1, 2, 3, 4, 6, 7 and 11) are known to be expressed at distinct sites along the nephron [1]. AQP1 and AQP2 have been identified in the urine. Aquaporin-1 is expressed in the proximal tubule, descending thin limb, and descending vasa recta cells, contributing to water reabsorption in the proximal tubules and formation of a renal osmotic gradient. Aquaporin-2 is expressed mainly at the apical membrane and intracellular vesicles in the collecting duct principal cells. Apical membrane expression of AQP2 is known to be regulated by arginine vasopressin (AVP), an antidiuretic hormone [2]
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