Laboratory Investigation

Kidney International (1989) 36, 960–968; doi:10.1038/ki.1989.288

In vitro modulation of tubular cyst regression in murine polycystic kidney disease

Ellis D Avner, William E Sweeney Jr and Demetrius Ellis

Department of Pediatrics, Children's Hospital of Pittsburgh and the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and the Department of Pediatrics, Children's Hospital Medical Center and the University of Washington School of Medicine, Seattle, Washington, USA

Correspondence: Ellis D Avner MD, Division of Nephrology, Children's Hospital and Medical Center, 4800 Sand Point Way, N.E., P.O. Box C-5371, Seattle, Washington 98105, USA.

Received 2 September 1987; Revised 20 June 1989; Accepted 6 July 1989.

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Abstract

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.

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