Plasma leakage through glomerular basement membrane ruptures triggers the proliferation of parietal epithelial cells and crescent formation in non-inflammatory glomerular injury.
Summary of "Plasma leakage through glomerular basement membrane ruptures triggers the proliferation of parietal epithelial cells and crescent formation in non-inflammatory glomerular injury."
Glomerular crescents are most common in rapidly progressive glomerulonephritis but also occur in non-inflammatory chronic glomerulopathies, thus, factors other than inflammation should trigger crescent formation, e.g. 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, 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 was 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 program 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 a cellular inflammation and rupture of the Bowman's capsule. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Germany.
This article was published in the following journal.
Name: The Journal of pathology
Medical and Biotech [MESH] Definitions
A type of glomerulonephritis that is characterized by the accumulation of immune deposits (COMPLEMENT MEMBRANE ATTACK COMPLEX) on the outer aspect of the GLOMERULAR BASEMENT MEMBRANE. It progresses from subepithelial dense deposits, to basement membrane reaction and eventual thickening of the basement membrane.
Glomerular Basement Membrane
The layer of EXTRACELLULAR MATRIX that lies between the ENDOTHELIUM of the glomerular capillaries and the PODOCYTES of the inner or visceral layer of the BOWMAN CAPSULE. It is the product of these two cell types. It acts as a physical barrier and an ion-selective filter.
Anti-glomerular Basement Membrane Disease
An autoimmune disease of the KIDNEY and the LUNG. It is characterized by the presence of circulating autoantibodies targeting the epitopes in the non-collagenous domains of COLLAGEN TYPE IV in the basement membranes of kidney glomeruli (KIDNEY GLOMERULUS) and lung alveoli (PULMONARY ALVEOLI), and the subsequent destruction of these basement membranes. Clinical features include pulmonary alveolar hemorrhage and glomerulonephritis.
Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.
Glomerular Filtration Rate
The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.
Thin basement membrane disease (TBMD) typically presents with persistent microscopic hematuria, and is usually defined as a glomerular basement membrane (GBM) thickness
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