2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smeets, B. Articles by Steenbergen, E. J. Search for Related Content PubMed PubMed Citation Articles by Smeets, B. Articles by Steenbergen, E. J.

The Parietal Epithelial Cell: A Key Player in the Pathogenesis of Focal Segmental Glomerulosclerosis in Thy-1.1 Transgenic Mice

Bart Smeets^*, Nathalie A.J.M. Te Loeke^*, Henry B.P.M. Dijkman^*, Mark L.M. Steenbergen^*, Joost F.M. Lensen, Mark P.V. Begieneman^*, Toin H. van Kuppevelt, Jack F.M. Wetzels and Eric J. Steenbergen^*

Departments of *Pathology, Nephrology, and Biochemistry, University Medical Center Nijmegen, Nijmegen, the Netherlands.

Correspondence to Dr. B. Smeets, Department of Pathology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. Phone: 31-24-3614326; Fax: 31-24-3540520; E-mail: b.smeets{at}pathol.umcn.nl

ABSTRACT. Focal segmental glomerulosclerosis (FSGS) is a hallmark of progressive renal disease. Podocyte injury and loss have been proposed as the critical events that lead to FSGS. In the present study, the authors have examined the development of FSGS in Thy-1.1 transgenic (tg) mice, with emphasis on the podocyte and parietal epithelial cell (PEC). Thy-1.1 tg mice express the Thy-1.1 antigen on podocytes. Injection of anti-Thy-1.1 mAb induces an acute albuminuria and development of FSGS lesions that resemble human collapsing FSGS. The authors studied FSGS lesions at days 1, 3, 6, 7, 10, 14, and 21, in relation to changes in the expression of specific markers for normal podocytes (WT-1, synaptopodin, ASD33, and the Thy-1.1 antigen), for mouse PEC (CD10), for activated podocytes (desmin), for macrophages (CD68), and for proliferation (Ki-67). The composition of the extracellular matrix (ECM) that forms tuft adhesions or scars was studied using mAb against collagen IV 2 and 4 chains and antibodies directed against different heparan sulfate species. The first change observed was severe PEC injury at day 1, which increased in time, and resulted in denuded segments of Bowman’s capsule at days 6 and 7. Podocytes showed foot process effacement and microvillous transformation. There was no evidence of podocyte loss or denudation of the GBM. Podocytes became hypertrophic at day 3, with decreased expression of ASD33 and synaptopodin and normal expression of WT-1 and Thy-1.1. Podocyte bridges were formed by attachment of hypertrophic podocytes to PEC and podocyte apposition against denuded segments of Bowman’s capsule. At day 6, there was a marked proliferation of epithelial cells in Bowman’s space. These proliferating cells were negative for desmin and all podocyte markers, but stained for CD10, and thus appeared to be PEC. The staining properties of the early adhesions were identical to that of Bowman’s capsule, suggesting that the ECM in the adhesions was produced by PEC. In conclusion, the authors propose the following sequence of events leading to FSGS lesions in the Thy1.1 tg mice: (1) PEC damage and denudation of Bowman’s capsule segments; (2) podocyte hypertrophy and bridging; and (3) PEC proliferation with ECM production.

This article has been cited by other articles:

				O. M. Steinmetz, U. Panzer, S. Fehr, C. Meyer-Schwesinger, R. A. K. Stahl, and U. O. Wenzel A pitfall of glomerular sieving: profibrotic and matrix proteins derive from the Bowman's capsule and not the glomerular tuft in rats with renovascular hypertension Nephrol. Dial. Transplant., October 1, 2007; 22(10): 3055 - 3060. [Abstract] [Full Text] [PDF]

				B. Smeets, M. L. M. Steenbergen, H. B. P. M. Dijkman, K. N. Verrijp, N. A. J. M. te Loeke, J. Aten, E. J. Steenbergen, and J. F. M. Wetzels Angiotensin converting enzyme inhibition prevents development of collapsing focal segmental glomerulosclerosis in Thy-1.1 transgenic mice Nephrol. Dial. Transplant., November 1, 2006; 21(11): 3087 - 3097. [Abstract] [Full Text] [PDF]

				M. Albaqumi, T. J. Soos, L. Barisoni, and P. J. Nelson Collapsing Glomerulopathy J. Am. Soc. Nephrol., October 1, 2006; 17(10): 2854 - 2863. [Abstract] [Full Text] [PDF]

				N. P.J. Vogtlander, H. Dijkman, M. A.H. Bakker, K. P. Campbell, J. van der Vlag, and J. H.M. Berden Localization of {alpha}-Dystroglycan on the Podocyte: from Top to Toe J. Histochem. Cytochem., November 1, 2005; 53(11): 1345 - 1353. [Abstract] [Full Text] [PDF]

				L. Barisoni, M. P. Madaio, M. Eraso, D. L. Gasser, and P. J. Nelson The kd/kd Mouse Is a Model of Collapsing Glomerulopathy J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2847 - 2851. [Abstract] [Full Text] [PDF]

				T. Asano, F. Niimura, I. Pastan, A. B. Fogo, I. Ichikawa, and T. Matsusaka Permanent Genetic Tagging of Podocytes: Fate of Injured Podocytes in a Mouse Model of Glomerular Sclerosis J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2257 - 2262. [Abstract] [Full Text] [PDF]

				T. Matsusaka, J. Xin, S. Niwa, K. Kobayashi, A. Akatsuka, H. Hashizume, Q.-c. Wang, I. Pastan, A. B. Fogo, and I. Ichikawa Genetic Engineering of Glomerular Sclerosis in the Mouse via Control of Onset and Severity of Podocyte-Specific Injury J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1013 - 1023. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673