Virchows Archiv

, Volume 445, Issue 3, pp 305–314

The dysregulated glomerular cell growth in Denys–Drash syndrome

Original Article

DOI: 10.1007/s00428-004-1069-2

Cite this article as:
Yang, A.H., Chen, J.Y. & Chen, B.F. Virchows Arch (2004) 445: 305. doi:10.1007/s00428-004-1069-2

Abstract

While diffuse mesangial sclerosis is traditionally described as being the glomerulopathy of Denys–Drash syndrome (DDS), the podocyte proliferative lesions may be overlooked in these DDS cases. In the present study, an evolving process is extrapolated from a selected case of DDS that demonstrated glomerulopathy with conspicuous podocyte proliferation. The observation that podocytes express proliferation markers (Ki67, proliferating-cell nuclear antigen and topoisomerase IIα) in non-proliferative, mature-looking glomeruli suggests an initial pathogenic act to activate or to keep podocytes from quiescence. The subsequent proliferation of podocytes is in keeping with downregulation of WT1 and cyclin kinase inhibitors of p16 and p21. The emergence of cytokeratin-positive cells in glomeruli that show typical mesangial sclerosis implies elimination of podocytes and replacement with tubular and/or parietal epithelial cells. The final scene of evolving glomerulopathy displays apoptosis and expression of Fas-L and Bax in sclerotic mesangial lesions, which eventually end up with global sclerosis. This novel concept of DDS glomerulopathy implies complex molecular mechanisms involved in glomerular injury.

Keywords

Denys–Drash syndrome Glomerulopathy Cyclin Cyclin kinase inhibitor Podocyte Apoptosis WT1 

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Ultrastructural and Molecular Pathology, Department of PathologyTaipei Veterans General HospitalTaipei Taiwan
  2. 2.Department of NephrologyTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Department of PathologyMcKay Memorial HospitalTaipeiTaiwan
  4. 4.Department of PathologySchool of Medicine, National Yang-Ming UniversityTaipeiTaiwan

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