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Am J Physiol Renal Physiol 275: F928-F937, 1998;
0363-6127/98 $5.00
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Vol. 275, Issue 6, F928-F937, December 1998

Kid-1 expression is high in differentiated renal proximal tubule cells and suppressed in cyst epithelia

Ralph Witzgall1, Nicholas Obermüller2, Ulrike Bölitz1, James P. Calvet3, Benjamin D. Cowley Jr.3, Cheryl Walker4, Wilhelm Kriz1, Norbert Gretz2, and Joseph V. Bonventre5

1 Institute of Anatomy and Cell Biology I, University of Heidelberg, 69120 Heidelberg; 2 Medical Research Center, Klinikum Mannheim, University of Heidelberg, 68167 Mannheim, Germany; 3 Kansas University Medical Center, Kansas City, Kansas 66160; 4 University of Texas M. D. Anderson Cancer Center, Smithville, Texas 78957; and 5 Renal Unit and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129

The cDNA coding for the transcriptional repressor protein Kid-1 was cloned in a screen for zinc finger proteins, which are regulated during renal development and after renal ischemia. Kid-1 mRNA levels increase in the course of postnatal renal development and decrease after acute renal injury caused by ischemia or administration of folic acid. We have raised a monoclonal anti-Kid-1 antibody and demonstrate that the Kid-1 protein is strongly expressed in the proximal tubule of the adult rat kidney. During nephron development, the Kid-1 protein appears after the S-shaped body stage concomitantly with the brush-border enzyme alkaline phosphatase. In two animal models of polycystic kidney disease, the expression of Kid-1 is downregulated. The loss of expression of Kid-1 in cyst wall cells correlates with the loss of alkaline phosphatase histochemical staining. Kid-1 mRNA levels are also reduced in rodent renal cell carcinomas, another condition characterized by epithelial cell dedifferentiation and increased proliferation. We propose that Kid-1 plays an important role during the differentiation of the proximal tubule.

renal development; renal cell carcinoma; polycystic kidney disease; gene regulation; transcriptional repression


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