Open AccessA bell‐shaped pattern of urinary aquaporin‐2‐bearing extracellular vesicle release in an experimental model of nephronophthisis
Author(s) -
Mikoda Nobuyuki,
Sonoda Hiroko,
Oshikawa Sayaka,
Hoshino Yuya,
Matsuzaki Toshiyuki,
Ikeda Masahiro
Publication year - 2019
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.14092
Subject(s) - aquaporin 2 , kidney , nephronophthisis , urinary system , medicine , endocrinology , biology , chemistry , gene , water channel , genetics , inlet , phenotype , mechanical engineering , engineering
The DBA /2‐ FG pcy (pcy) mouse is a model of human nephronophthisis, a recessive cystic kidney disease. Renal expression of aquaporin‐2 ( AQP 2), a water channel protein, has been shown to be altered in pcy mice. However, the relationship between the renal expression and its release in urinary extracellular vesicles ( uEV ‐ AQP 2), which account for most urinary AQP 2, in pcy mice has remained largely unknown. In this study, we examined age‐related alterations of this relationship in pcy mice. In comparison with control mice, pcy mice after the age of 14 weeks showed defective urinary concentration ability with an increase in urinary volume. Interestingly, the release of uEV ‐ AQP 2 increased progressively up to the age of 16 weeks, but at 21 weeks the release did not significantly differ from that in control mice (i.e., a bell‐shaped pattern was evident). Similar results were obtained for uEV marker proteins, including tumor susceptibility gene 101 ( TSG 101) protein and apoptosis‐linked gene 2‐interacting protein X (Alix). Immunoblot analysis revealed that renal AQP 2 expression increased progressively from 11 weeks, and immunohistochemistry showed that this increase was possibly due to an increase in the number of AQP 2‐positive cells. Analysis of mRNA s for seven types of AQP expressed in the kidney supported this notion. These data suggest that the level of uEV ‐ AQP 2 does not simply mirror the renal expression of AQP 2 and that the altered release of uEV ‐ AQP 2 in pcy mice depends on the numbers of both renal AQP 2‐positive cells and EV s released into the urine.