In vitro modulation of tubular cyst regression in murine polycystic kidney disease.
Recent studies in a murine model of genetically-determined polycystic kidney disease, the CPK mouse, have suggested that alterations in renal Na-K ATPase activity in concert with tubular epithelial hyperplasia have pathogenic import in proximal tubular cyst formation. In the current study, we therefore studied the relative roles of Na-K ATPase activity, tubular epithelial hyperplasia, and basal lamina alterations during in vitro modulation of proximal tubular cyst regression during serum-free organ culture of newborn CPK kidneys. Under basal in vitro conditions, regression of CPK proximal tubular cysts was demonstrated in association with progressive decreases in Na-K ATPase activity and tubular epithelial hyperplasia. The pattern of proximal tubular cyst regression was modified by: a) Na-K ATPase activity induction with triiodothyronine, which promoted proximal tubular cystogenesis; and b) Na-K ATPase activity inhibition with ouabain, which blocked the effects of T3 on the process of cyst formation. Modulation of proximal tubular cystogenesis by Na-K ATPase induction and inhibition were accomplished without significant changes in proximal tubular epithelial hyperplasia or expression of basal lamina components. We conclude that increased Na pump activity may have a significant role in proximal tubular cyst formation and progressive enlargement in the CPK mouse.
Avner
E D
ED
Department of Pediatrics, Children's Hospital of Pittsburgh, Pennsylvania.
Sweeney
W E
WE
Ellis
D
D
D000818:Animals; D004848:Epithelium / Q000473:pathology; D006965:Hyperplasia; D007684:Kidney Tubules / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D007690:Polycystic Kidney Diseases / Q000209:etiology / Q000473:pathology*; D015222:Sodium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D015222:Sodium Channels; D000254:Sodium-Potassium-Exchanging ATPase