The PAX2 tanscription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations

J Clin Invest. 1996 Jul 15;98(2):451-9. doi: 10.1172/JCI118811.


Human dysplastic kidneys are developmental aberrations which are responsible for many of the very young children with chronic renal failure. They contain poorly differentiated metanephric cells in addition to metaplastic elements. We recently demonstrated that apoptosis was prominent 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 tendency of some of these organs to regress. In contrast, apoptosis was rare in dysplastic epithelia which are thought to be ureteric bud malformations. On occasion, these tubules form cysts which distend the abdominal cavity (the multicystic dysplastic kidney) and dysplastic kidneys may rarely become malignant. We now demonstrate that dysplastic tubules maintain a high rate of proliferation postnatally and that PAX2, a potentially oncogenic transcription factor, is expressed in these epithelia. In contrast, both cell proliferation and PAX2 are downregulated during normal maturation of human collecting ducts. We demonstrate that BCL2, a protein which prevents apoptosis in renal mesenchymal to epithelia] conversion, is expressed ectopically in dysplastic kidney epithelia. We propose that dysplastic cyst formation may be understood in terms of aberrant temporal and spatial expression of master genes which are tightly regulated in the normal program of human nephrogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / biosynthesis*
  • Female
  • Fetus
  • Gene Expression*
  • Gestational Age
  • Humans
  • Immunohistochemistry
  • Infant
  • Kidney / abnormalities*
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney Diseases, Cystic / metabolism*
  • Kidney Diseases, Cystic / pathology
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / pathology
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Male
  • PAX2 Transcription Factor
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2
  • Reference Values
  • Sudden Infant Death
  • Transcription Factors / analysis
  • Transcription Factors / biosynthesis*
  • WT1 Proteins
  • Wilms Tumor / metabolism*
  • Wilms Tumor / pathology


  • DNA-Binding Proteins
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factors
  • WT1 Proteins