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Expression of aquaporin 1 (AQP1) along the mammalian nephron : sex and species differences

In the mammalian kidneys, AQP1 is supposed to be a constitutive water channel located in the apical and basolateral domain of proximal tubule (PT) and descending thin limb (DTL) epithelium. In the membrane it exists in two, nonglycosylated (NG, ~28 kDa) and glycosylated (G, 40-50 kDa) forms, both being water permeable. Factors influencing renal AQP1 expression in (patho)physiological conditions are poorly known ; thus far only angiotensin II and hypertension were found to upregulate its protein and mRNA expression in the rat PT (Am J Physiol Renal Physiol 297:F1575, 2009). In order to investigate possible sex and species differences in the expression of renal AQP1, we used an anti-AQP1 polyclonal antibody and performed immunocytochemistry on tissue cryosections and Western blotting (WB) of cell membranes isolated from various kidney zones of adult male (M) and female (F) rats, mice, pigs and humans. Effects of sex hormones on AQP1 expression were studied more thoroughly in prepubertal and adult, gonadectomized and sex hormone-treated gonadectomized rats. In rats and mice, the AQP1-related immunostaining in various kidney zones in M was stronger than in F, whereas the expression (immunostaining intensity) of AQP1 in the pig and human kidneys of both sexes was similar. These results were confirmed by WB of total cell membranes (TCM), and brush-border and basolateral membranes isolated from the respective kidney zones. The observed sex differences in expression were comparable for both NG and G forms of AQP1. In the adult rats, castration had no effect, while ovariectomy increased the abundance of AQP1 in the renal TCM. Furthermore, treatment of castrated animals with testosterone upregulated, whereas treatment with estradiol and progesterone had no significant effect on NG and G forms of AQP1. Strong, but sex-independent AQP1 expression was detected in red blood cell membranes isolated from adult rats, whereas in TCM isolated from the kidneys of prepubertal rats, the AQP1 expression was weak and similar in both sexes. We conclude that a) sex differences exist in the expression of AQP1 along the nephron of adult rats and mice (M > F), which result from both upregulating effects of androgens in M and downregulating effects of estrogens in F after the puberty, and b) similar sex differences are absent in the pig and human kidneys, thus indicating the presence of species differences in the expression of renal AQP1.

aquaporin 1; mammalian kidney; sex differences; species differences

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