Expression of aquaporins 1 and 2 during nephrogenesis and in
autosomal dominant polycystic kidney disease.
Devuyst, Olivier, Christopher R. Burrow, Barbara L. Smith, Peter Agre,
Mark A. Knepper, and Patricia D. Wilson.
Division of Nephrology, and Departments of Medicine and Biological
Chemistry, The Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205; and Laboratory of Kidney and Electrolyte
Metabolism, National Heart, Lung and Blood Institute, National
Institute of Health, Bethesda, Maryland 20892-1598
APStracts 3:0003F, 1996.
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 (12wk gestation). AQP1 was first
seen in developing PT epithelia, predominantly in apical cell
membranes, and at 15wk was also detected in DTL. AQP2 was seen in
apical cell membranes of the branching ureteric bud and CD system
from 12wk and throughout development. In adult normal kidneys, AQP1
was localized to apical and basolateral membrane domains of PT and
DTL, while 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 endstage ADPKD, two-thirds of the cysts expressed
either AQP1 or AQP2, but these two water channels were never co
-localized 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 (i) demonstrate specific, mutually
exclusive localization of AQP1 and AQP2 in human fetal and adult
kidneys; (ii) show that both channels are expressed early during
nephrogenesis; (iii) show that the mutual exclusivity of localization
is maintained even into endstage ADPKD.
Received 3 August 1995; accepted in final form 14 December 1995.
APS Manuscript Number F254-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96