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Renal Progenitor Cells Contribute to Hyperplastic Lesions of Podocytopathies and Crescentic Glomerulonephritis

Bart Smeets^*,, Maria Lucia Angelotti, Paola Rizzo, Henry Dijkman^*, Elena Lazzeri, Fieke Mooren^*, Lara Ballerini, Eliana Parente, Costanza Sagrinati, Benedetta Mazzinghi, Elisa Ronconi, Francesca Becherucci, Ariela Benigni, Eric Steenbergen^*, Laura Lasagni, Giuseppe Remuzzi^,||, Jack Wetzels^¶ and Paola Romagnani

Departments of *Pathology and
^¶Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands;
Division of Nephrology and Immunology, University Hospital of the Aachen University of Technology (RWTH), Aachen, Germany;
Excellence Center for Research, Transfer and High Education DENOTHE, University of Florence, Florence, Italy;
Mario Negri Institute for Pharmacological Research, Bergamo, Italy; and
^||Unit of Nephrology and Dialysis, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy

Correspondence: Dr. Paola Romagnani, Department of Clinical Pathophysiology, Nephrology Section, University of Florence, Viale Pieraccini 6, 50139, Firenze, Italy. Phone: ++39554271356; Fax: ++39554271357; E-mail: p.romagnani{at}dfc.unifi.it or Dr. Bart Smeets, Department of Pathology, Radboud University Nijmegen Medical Center, Geert Grooteplein 24, 6500 HB Nijmegen, Netherlands. Phone: 00492418088592; Fax: 00492418082446; E-mail: b.smeets{at}pathol.umcn.nl

Received for publication February 2, 2009. Accepted for publication September 16, 2009.

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase–PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133⁺CD24⁺podocalyxin (PDX)^–nestin^– renal progenitors, CD133⁺CD24⁺PDX⁺nestin⁺ transitional cells, and CD133^–CD24^–PDX⁺nestin⁺ differentiated podocytes. In addition, TGF-β induced CD133⁺CD24⁺ progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

This article has been cited by other articles:

				B. Smeets, S. Uhlig, A. Fuss, F. Mooren, J. F.M. Wetzels, J. Floege, and M. J. Moeller Tracing the Origin of Glomerular Extracapillary Lesions from Parietal Epithelial Cells J. Am. Soc. Nephrol., December 1, 2009; 20(12): 2604 - 2615. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673