WATER CHANNEL EXPRESSION IN HUMAN ADPKD KIDNEYS

Cyst enlargement in autosomal dominant polycystic kidney disease (ADPK D) results in part from the transport of solute and fluid into the lum en of the cyst. In proximal tubules and thin descending limbs of norma l kidneys, the high transepithelial water permeability of these segmen ts is due to the presence of the water channel protein, aquaporin-CHIP (AQP-CHIP, i.e., AQP-1). The collecting ducts of normal kidneys expre ss another member of this gene family, the aquaporin collecting duct ( AQP-CD, i.e., AQP-2). The expression and distribution of these two mem bers of the aquaporin gene family were examined in ADPKD and normal hu man kidneys. In both tissues, Western blotting with the anti-AQP-CHIP antibody revealed a major 28-kDa band. By immunofluorescence, AQP-CHIP was present in proximal tubules and thin descending limbs of Henle of both normal and ADPKD kidneys. In the latter, AQP-CHIP was detected i n the epithelia lining 71% of cysts. Many cysts were positive for the proximal tubule marker gp330 (44%). Some cysts expressing AQP-CHIP did not stain for gp330, suggesting a descending thin limb origin, and a few cysts were negative for both markers. In normal human kidney, West ern blotting with the anti-AQP-CD antibody revealed a band at 28 kDa. AQP-CD was localized to collecting ducts and did not show colocalizati on with gp330 in normal human kidney. In ADPKD kidney, AQP-CD was expr essed by only 8% of cysts. In summary, water channels, primarily AQP-C HIP, are expressed in epithelial cells Lining cysts in similar to 80% of cysts in ADPKD kidneys. This finding suggests the possibility that water channels could play a role in fluid movement into cyst lumina.