C5b–9 and adhesion molecules in human idiopathic membranous nephropathy

Papagianni, Αikaterini; Alexopoulos, Efstathios; Leontsini, Maria; Papadimitriou, M.

doi:10.1093/ndt/17.1.57

Cited by 21 publications

(24 citation statements)

References 19 publications

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“…The pathologic changes from renal tissues of Thy-1 N are dependent on complement activation and independent on neutrophil influx (Yamamoto and Wilson, 1987;Brandt et al, 1996). Because recent studies have confirmed that the role of C5b-9 to resident glomerular cells belongs to non-lytic (sublytic) in the majority (Couser et al, 2001;Papagianni et al, 2002;Nauta et al, 2002), deeply exploring the effects of sublytic C5b-9 in Thy-1 N has become a subject of intense inquiry (Pippin et al, 2003;Shimizu et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric oxide synthesis

Wang

Qin

et al. 2006

Life Sciences

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Section: Discussionmentioning

confidence: 99%

The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric oxide synthesis

Wang

Qin

et al. 2006

Life Sciences

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“…Such acquired CR1 deficiency could increase the susceptibility of podocytes to complement activation by antibodies in subepithelial immune deposits (82). As in experimental MN, C5b-9 is assembled on the podocytes of patients with MN, which is evident histologically (26,99) and by examining urine for C5b-9 (65,125). Complicating the utility of urinary C5b-9 measurement is alternative complement pathway activation on proximal tubular cells noted previously, which also can result in the appearance of C5b-9 in the urine of proteinuric patients, including those with MN (85,96).…”

Section: Implications For Human Mnmentioning

confidence: 98%

“…Still, there is a good deal of circumstantial evidence that complement is activated in subepithelial immune deposits, including the presence of C3 and C5b-9 in many cases (48,99) and C3d in all cases of human MN (28); C3d is the stable C3 product generated from iC3b by factor I, presumably relying on podocyte CR1 as a cofactor. Despite these apparent contradictions, it does seem likely that in human MN complement activation is initiated through the classical pathway with possible amplification by the alternative pathway, a scenario that may be more common than previously appreciated (51).…”

Section: Implications For Human Mnmentioning

confidence: 99%

Experimental membranous nephropathy redux

Cybulsky

Quigg²,

Salant³

2005

American Journal of Physiology-Renal Physiology

116

133

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Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Active and passive Heymann nephritis (HN) in rats are valuable experimental models because their features so closely resemble human MN. In HN, subepithelial immune deposits form in situ as a result of circulating antibodies. Complement activation leads to assembly of C5b-9 on glomerular epithelial cell (GEC) plasma membranes and is essential for sublethal GEC injury and the onset of proteinuria. This review revisits HN and focuses on areas of substantial progress in recent years. The response of the GEC to sublethal C5b-9 attack is not simply due to disruption of the plasma membrane but is due to the activation of specific signaling pathways. These include activation of protein kinases, phospholipases, cyclooxygenases, transcription factors, growth factors, NADPH oxidase, stress proteins, proteinases, and others. Ultimately, these signals impact on cell metabolic pathways and the structure/function of lipids and key proteins in the cytoskeleton and slit-diaphragm. Some signals affect GEC adversely. Thus C5b-9 induces partial dissolution of the actin cytoskeleton. There is a decline in nephrin expression, reduction in F-actin-bound nephrin, and loss of slit-diaphragm integrity. Other signals, such as endoplasmic reticulum stress, may limit complement-induced injury, or promote recovery. The extent of complement activation and GEC injury is dependent, in part, on complement-regulatory proteins, which act at early or late steps within the complement cascade. Identification of key steps in complement activation, the cellular signaling pathways, and the targets will facilitate therapeutic intervention in reversing GEC injury in human MN.

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“…Sublethal complement activation occurs on affected podocytes, causing damage and intracellular signaling activation (162,35). It has been well documented that deposition of the terminal components of complement (c5b-9) occurs not only in PHN (3,33,82,135,147) but also in MN in humans (30,49,91,131,133). Moreover, c5b-9 is required in some models of PHN (9,34,124,135).…”

Section: Rat Model Of Passive Heymann Nephritismentioning

confidence: 99%

Inducible rodent models of acquired podocyte diseases

Pippin

Brinkkoetter²,

Cormack-Aboud³

et al. 2009

American Journal of Physiology-Renal Physiology

236

263

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Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, Durvasula RV, Hauser PV, Kowalewska J, Krofft RD, Logar CM, Marshall CB, Ohse T, Shankland SJ. Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol 296: F213-F229, 2009. First published September 10, 2008 doi:10.1152/ajprenal.90421.2008.-Glomerular diseases remain the leading cause of chronic and end-stage kidney disease. Significant advances in our understanding of human glomerular diseases have been enabled by the development and better characterization of animal models. Diseases of the glomerular epithelial cells (podocytes) account for the majority of proteinuric diseases. Rodents have been extensively used experimentally to better define mechanisms of disease induction and progression, as well as to identify potential targets and therapies. The development of podocyte-specific genetically modified mice has energized the research field to better understand which animal models are appropriate to study acquired podocyte diseases. In this review we discuss inducible experimental models of acquired nondiabetic podocyte diseases in rodents, namely, passive Heymann nephritis, puromycin aminonucleoside nephrosis, adriamycin nephrosis, liopolysaccharide, crescentic glomerulonephritis, and protein overload nephropathy models. Details are given on the model backgrounds, how to induce each model, the interpretations of the data, and the benefits and shortcomings of each. Genetic rodent models of podocyte injury are excluded.glomerulus; animal models HISTOLOGICAL ANALYSIS is a cornerstone for studying mechanisms of glomerular disease. However, analysis in human disease is limited by a relative paucity of tissue availability. Renal biopsies are only pursued if a presumptive diagnosis cannot be established on clinical grounds. Tissue sampling is typically restricted to the time of disease presentation and is rarely performed in follow-up, providing a mere snapshot of disease course.Animal models have significantly advanced our understanding of the pathogenesis of glomerular disease by overcoming these hurdles. Serial assessment of renal tissue in experimental models affords the opportunity to study development and progression of disease over time. Furthermore, the host response to injury may be deliberately modified, for example, through pharmacological intervention, selective disruption (knockout strategies), or overexpression (transgenic strategies) of a particular gene, allowing for mechanistic evaluations. A variety of animal species have been employed in the study of glomerular disease, but rodent models are preferred due to lower cost, maintenance requirements, and short gestational periods. Although both rats and mice are utilized, there are some important advantages and disadvantages for each (Table 1). The development of transgenic technology has proven an invaluable tool in elucidating the function of individual genes in health and disease. However, they cannot replace experimental models in furthering our understanding of the mechanisms...

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C5b–9 and adhesion molecules in human idiopathic membranous nephropathy

Cited by 21 publications

References 19 publications

The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric oxide synthesis

The complement C5b-9 complexes induced injury of glomerular mesangial cells in rats with Thy-1 nephritis by increasing nitric oxide synthesis

Experimental membranous nephropathy redux

Inducible rodent models of acquired podocyte diseases

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