Universität zu Köln

Ryu, Mi, Migliorini, Adriana, Miosge, Nicolai, Gross, Oliver, Shankland, Stuart, Brinkkoetter, Paul T., Hagmann, Henning, Romagnani, Paola ORCID: 0000-0002-1774-8088, Liapis, Helen and Anders, Hans-Joachim ORCID: 0000-0003-2434-2956 (2012). Plasma leakage through glomerular basement membrane ruptures triggers the proliferation of parietal epithelial cells and crescent formation in non-inflammatory glomerular injury. J. Pathol., 228 (4). S. 482 - 495. HOBOKEN: WILEY. ISSN 1096-9896

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Abstract

Glomerular crescents are most common in rapidly progressive glomerulonephritis but also occur in noninflammatory chronic glomerulopathies; thus, factors other than inflammation should trigger crescent formation, eg vascular damage and plasma leakage. Here we report that Alport nephropathy in Col4A3-deficient Sv129 mice is complicated by diffuse and global crescent formation in which proliferating parietal epithelial cells are the predominant cell type. Laminin staining and transmission and acellular scanning electron microscopy of acellular glomeruli documented disruptions and progressive disintegration of the glomerular basement membrane in Col4A3-deficient mice. FITC-dextran perfusion further revealed vascular leakage from glomerular capillaries into Bowman's space, further documented by fibrin deposits in the segmental crescents. Its pathogenic role was validated by showing that the fibrinolytic activity of recombinant urokinase partially prevented crescent formation. In addition, in vitro studies confirmed an additional mitogenic potential of serum on murine and human parietal epithelial cells. Furthermore, loss of parietal cell polarity and unpolarized secretion of extracellular matrix components were evident within fibrocellular crescents. Among 665 human Alport nephropathy biopsies, crescent formation was noted in 0.4%. We conclude that glomerular vascular injury and GBM breaks cause plasma leakage which triggers a wound healing programme involving the proliferation of parietal cells and their loss of polarity. This process can trigger cellular and fibrocellular crescent formation even in the absence of cellular inflammation and rupture of the Bowman's capsule. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ryu, Mi UNSPECIFIED UNSPECIFIED UNSPECIFIED Migliorini, Adriana UNSPECIFIED UNSPECIFIED UNSPECIFIED Miosge, Nicolai UNSPECIFIED UNSPECIFIED UNSPECIFIED Gross, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Shankland, Stuart UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkkoetter, Paul T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagmann, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Romagnani, Paola UNSPECIFIED orcid.org/0000-0002-1774-8088 UNSPECIFIED Liapis, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Anders, Hans-Joachim UNSPECIFIED orcid.org/0000-0003-2434-2956 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-478039
DOI:	10.1002/path.4046
Journal or Publication Title:	J. Pathol.
Volume:	228
Number:	4
Page Range:	S. 482 - 495
Date:	2012
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1096-9896
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALPORTS-SYNDROME; MOUSE MODEL; MYOFIBROBLAST TRANSDIFFERENTIATION; INTERSTITIAL MACROPHAGES; STEM-CELLS; MICE; GLOMERULOSCLEROSIS; PODOCYTES; BLOCKADE; FIBROSIS Multiple languages Oncology; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47803