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, Paola Romagnani

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Abstract

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.

Original languageEnglish
Pages (from-to)2593-2603
Number of pages11
JournalJournal of the American Society of Nephrology
Volume20
Issue number12
DOIs
Publication statusPublished - Dec 1 2009

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ASJC Scopus subject areas

  • Nephrology

Cite this

Smeets, B., Angelotti, M. L., Rizzo, P., Dijkman, H., Lazzeri, E., Mooren, F., Ballerini, L., Parente, E., Sagrinati, C., Mazzinghi, B., Ronconi, E., Becherucci, F., Benigni, A., Steenbergen, E., Lasagni, L., Remuzzi, G., Wetzels, J., & Romagnani, P. (2009). Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis. Journal of the American Society of Nephrology, 20(12), 2593-2603. https://doi.org/10.1681/ASN.2009020132