Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease

Abstract

Aquaporin-1 (AQP1), located in proximal tubules (PT) and descending thin limbs of Henle (DTL), and aquaporin-2 (AQP2), located in collecting ducts (CD), are channels involved in water transport across renal tubule epithelia. Using antibodies against AQP1 and AQP2, we here show expression of AQP1 and AQP2 in normal human developing and adult kidneys and in autosomal dominant polycystic kidney disease (ADPKD). Unlike in rats, AQP1 and AQP2 are expressed early during human nephrogenesis (12-wk gestation). AQP1 was first seen in developing PT epithelia, predominantly in apical cell membranes, and, at 15 wk, was also detected in DTL. AQP2 was seen in apical cell membranes of the branching ureteric bud and CD system from 12 wk and throughout development. In adult normal kidneys, AQP1 was localized to apical and basolateral membrane domains of PT and DTL, whereas AQP2 was restricted to principal cells of CD. This distribution of AQP1 and AQP2 was also seen in early stage ADPKD, except that AQP1 was mostly located in the apical membrane region of expanded PT. In end-stage ADPKD, two-thirds of the cysts expressed either AQP1 or AQP2, but these two water channels were never colocalized in the same cyst. Western blot analysis showed maximal expression of AQP1 and AQP2 in normal adult kidneys, lower levels in fetal kidneys, and decreases associated with degree of cystic progression in ADPKD. These data 1) demonstrate specific, mutually exclusive localization of AQP1 and AQP2 in human fetal and adult kidneys; 2) show that both channels are expressed early during nephrogenesis; and 3) show that the mutual exclusivity of localization is maintained even into end-stage ADPKD.