THE PAX2 TRANSCRIPTION FACTOR IS EXPRESSED IN CYSTIC AND HYPERPROLIFERATIVE DYSPLASTIC EPITHELIA IN HUMAN KIDNEY MALFORMATIONS

Human dysplastic kidneys are developmental aberrations which are respo nsible for many of the very young children with chronic renal failure. They contain poorly differentiated metanephric cells in addition to m etaplastic elements. We recently demonstrated that apoptosis was promi nent in undifferentiated cells around dysplastic tubules (Winyard, P.J .D., J. Nauta, D.S. Lirenman, P. Hardman, V.R. Sams, R.A. Risdon, and A.S. Woolf. 1996. Kidney Int. 49:135-146), perhaps explaining the tend ency of some of these organs to regress. In contrast, apoptosis was ra re in dysplastic epithelia which are thought to be ureteric bud malfor mations. On occasion, these tubules form cysts which distend the abdom inal cavity (the multicystic dysplastic kidney) and dysplastic kidneys may rarely become malignant. We now demonstrate that dysplastic tubul es maintain a high rate of proliferation postnatally and that PAX2, a potentially oncogenic transcription factor, is expressed in these epit helia. In contrast, both cell proliferation and PAX2 are downregulated during normal maturation of human collecting ducts. We demonstrate th at BCL2, a protein which prevents apoptosis in renal mesenchymal to ep ithelial conversion, is expressed ectopically in dysplastic kidney epi thelia. We propose that dysplastic cyst formation may be understood in terms of aberrant temporal and spatial expression of master genes whi ch are tightly regulated in the normal program of human nephrogenesis.