Laboratory Investigation

Kidney International (1992) 42, 89–94; doi:10.1038/ki.1992.265

Ureteral obstruction decreases renal prepro-epidermal growth factor and Tamm-Horsfall expression

Shimon Storch1, Subodh Saggi1, Judith Megyesi1, Peter M Price1 and Robert Safirstein1

1Renal Division, Department of Medicine and Department of Biochemistry, Mount Sinai School of Medicine, New York, New York, USA

Correspondence: Robert Safirstein MD, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, New York 10029, USA.

Received 6 May 1991; Revised 10 February 1992; Accepted 10 February 1992.

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Abstract

Ureteral obstruction decreases renal prepro-EGF and Tamm-Horsfall expression. Northern and dot-blot analysis of polyadenylated RNAs of kidney cortical and outer medullary tissue was performed in male Sprague-Dawley rats at varying times up to 24 hours after bilateral ureteral obstruction (BUO), after 24 hours of unilateral obstruction (UUO) and at varying periods after release of BUO or UUO. PreproEGF (preproEGF) and Tamm-Horsfall (TH) mRNA declined by four hours of BUO to virtually undetectable levels at 24 hours of ureteral obstruction. Upon release of BUO or UUO, preproEGF and TH mRNA returned slowly toward normal but remained below control levels up to four days after release of ureteral obstruction. Urinary EGF excretion paralleled these changes in renal preproEGF mRNA. Although these changes are similar to those observed during nephrotoxic and ischemic renal failure, where the expression of the immediate early genes precedes the fall in preproEGF and TH expression, no such increase in the expression of these genes occurred after bilateral ureteral obstruction. These changes in preproEGF and TH expression could also be dissociated from uremia and high rates of DNA synthesis, suggesting that ureteral obstruction itself is a sufficient cause of the reduced expression. The increase in ureteral pressure and its functional and humoral effects may each play a role in reduced preproEGF and TH expression during ureteral obstruction.

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