Abstract
Urinary exosomes, small extracellular vesicles present in urine, are secreted from all types of renal epithelial cells. Aquaporin-2 (AQP2), a vasopressin-regulated water channel protein, is known to be selectively excreted into the urine through exosomes (UE-AQP2), and its renal expression is decreased in nephrotic syndrome. However, it is still unclear whether excretion of UE-AQP2 is altered in nephrotic syndrome. In this study, we examined the excretion of UE-AQP2 in an experimental rat model of nephrotic syndrome induced by the administration of puromycin aminonucleoside (PAN). Rats were assigned to two groups: a control group administered saline and a PAN group given a single intraperitoneal injection of PAN (125 mg/kg) at day 0. The experiment was continued for 8 days, and samples of urine, blood, and tissue were collected on days 2, 5, and 8. The blood and urine parameters revealed that PAN induced nephrotic syndrome on days 5 and 8, and decreases in the excretion of UE-AQP2 were detected on days 2 through 8 in the PAN group. Immunohistochemistry showed that the renal expression of AQP2 was decreased on days 5 and 8. The release of exosomal marker proteins into the urine through UEs was decreased on day 5 and increased on day 8. These data suggest that UE-AQP2 is decreased in PAN-induced nephrotic syndrome and that this reflects its renal expression in the marked proteinuria phase after PAN treatment.
Highlights
Urinary exosomes (UEs) are tiny extracellular vesicles (
We investigated the excretion of UE-AQP2 in nephrotic syndrome using rats treated with puromycin aminonucleoside (PAN), as well as the release of exosomal marker proteins, including tumor susceptibility gene 101 protein (TSG101) and ALG-2 interacting protein X (ALIX) [8,20]
At the same time point, immunoblotting analysis of exosomal marker proteins suggested that the number of exosomes released into urine in the PAN group was unchanged relative to that in the control group
Summary
Urinary exosomes (UEs) are tiny extracellular vesicles (
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