Cell polarity in human renal cystic disease.
BACKGROUND
In polycystic kidney disease (PKD), altered cellular polarity with mislocation of Na/K-ATPase, and net fluid secretion may have a role in cyst development and progression.


METHODS
Cell polarity was assessed in surgically excised human normal, autosomal dominant PKD, and acquired PKD occurring in end stage renal disease on long-term dialysis kidneys quick frozen (< 5 minutes) or fixed to minimize ischemic changes.


RESULTS
Findings were similar in autosomal dominant PKD and acquired PKD kidneys. By ultrastructure, in cysts, cells were polarized, however, their basement membranes were greatly thickened and reticulated. By immunohistology, in cell-lining cysts, Na/K-ATPase, fodrin, and ankyrin were localized primarily to basolateral cell membranes and uvomorulin was localized to lateral cell membranes. In about 25% of the cells, however, Na/K-ATPase was localized to the apical as well as the basolateral membranes. Both in autosomal dominant PKD and normal kidney cell monolayers in vitro, cationic ferritin was normally absorbed by apical endocytosis, and transferred to apical vacuoles and phagolysosomes.


CONCLUSIONS
These findings indicate intact structural and functional polarity in cell-lining cysts; however, in about 25% of the cells, Na/K-ATPase, fodrin, and ankyrin are localized to apical and lateral cell membranes, probably due to cell dedifferentiation. The notable changes in the basement membranes of cysts suggest a key role for the extracellular matrix in the pathogenesis of PKD.
Carone
F A
FA
Department of Pathology, Northwestern University Medical School, Chicago, Illinois.
Nakamura
S
S
Caputo
M
M
Bacallao
R
R
Nelson
W J
WJ
Kanwar
Y S
YS
D000328:Adult; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005293:Ferritins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000601:surgery / Q000628:therapy; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008875:Middle Aged; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D012016:Reference Values; D006435:Renal Dialysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis
D008565:Membrane Proteins; D005293:Ferritins; D000254:Sodium-Potassium-Exchanging ATPase