Renal tubule Na,K-ATPase polarity in glucocorticoid-induced polycystic kidney disease.
Cyst formation in polycystic kidney disease (PKD) involves proliferation of cyst lining epithelial and changes in trans-epithelial fluid and electrolyte transport. In vitro studies have suggested that mislocation of Na,K-ATPase to the apical tubular surface may be an important component of cyst fluid transport. We undertook in vivo studies of Na,K-ATPase location using the "threshold" murine model of glucocorticoid-induced PKD (GIPKD). Using histological, immunohistochemical, and densitometric techniques, we compared cyst formation and the cellular location of Na,K-ATPase in suckling C3H (low threshold for GIPKD) and DBA (high threshold) mice given an inducing dose of 200 mg/kg methylprednisolone acetate. As expected, C3H mice demonstrated greater cyst formation as measured by proportion of section area occupied by the tubule lumen (26.7% vs 15.5%; p < 0.001). Cyst formation was associated with increased Na,K-ATPase staining and increased apical Na,K-ATPase location. MPA treatment in C3H mice resulted in apical staining that exceeded basolateral staining (35.3% of reference window vs 29.8%; p < 0.001). The relatively GIPKD-resistant DBA mice did not show such change in Na,K-ATPase location. These immunohistochemical studies suggest a role for Na,K-ATPase in renal cyst formation.
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
M R
MR
Ogborn
S
S
Sareen
P C
PC
Grimm
D000818:Animals; D016764:Cell Polarity; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D007684:Kidney Tubules / Q000201:enzymology*; D008775:Methylprednisolone / Q000031:analogs & derivatives; D000077555:Methylprednisolone Acetate; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D007690:Polycystic Kidney Diseases / Q000139:chemically induced / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis*
D000077555:Methylprednisolone Acetate; D000254:Sodium-Potassium-Exchanging ATPase; D008775:Methylprednisolone