Apoptosis and Proliferating Cell Nuclear Antigen in Lupus Nephritis (Class IV) and Membranoproliferative Glomerulonephritis

Kırım, Sinan; Tetıker, Tamer; Paydas, S; Gönlüşen, Gülfiliz

doi:10.1081/jdi-42724

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…This study revealed that quantifying apoptosis in renal biopsies predicts relatively little regarding future renal function. This is in agreement with a recent study which found no predictive value of apoptosis for renal function in patients with lupus nephritis or membranoproliferative GN [13]. Further studies using dynamic remodeling with apoptosis and proliferation of renal cells during the course of such diseases may explain why the apoptosis rate at biopsy provides only a very narrow insight into these long-term processes.…”

Section: Discussionsupporting

confidence: 77%

“…Some minor degree of apoptosis using detection of DNA fragmentation has been also described by other authors in apparently normal human kidney specimens [10]. Apoptosis of glomerular cells plays a role in IgA nephropathy and lupus nephritis, especially in the development of sclerotic glomeruli [10,11,12,13], but has been also reported in membranoproliferative GN, and FSGS [14, 15]. Savill [1] found that apoptosis is an important mechanism for the remodeling of glomeruli in proliferative GN in the anti-Thy 1.1 rat model, a model of reversible inflammatory proliferative GN.…”

Section: Discussionmentioning

confidence: 99%

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DNA Fragmentation in Chronic Glomerulonephritis: An Immunohistological Analysis

Ott¹,

Aschoff

Pocock³

et al. 2006

Nephron Clin Pract

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Background: Experimental data suggest that apoptosis plays an important pathophysiological role in glomerulonephritis by restoring tissue structure after proliferation of intrinsic renal cells and infiltration of leukocytes. Relatively little is known of apoptosis in human glomerulonephritis, particularly in predicting renal function during follow-up. Methods: In order to colocalize different markers for cell damage in renal tissue from patients with different forms of glomerulonephritis (GN), a series of semithin sections from 34 kidney biopsies were studied retrospectively. Normal kidney from a nephrectomy specimen with a small renal adenocarcinoma served as a control. DNA fragmentation, expression of tissue transglutaminase II, BAX and BCL-2 were visualized immunohistochemically. In some renal biopsies, immunohistochemical staining for activated caspase 3 was performed. Proinflammatory markers (C-reactive protein, leukocytes), serum creatinine, creatinine clearance, total proteinuria, albuminuria, α₁-microglobulin and IgG excretion were determined at the time of biopsy. Serum creatinine and total proteinuria were assessed 6 and 12 months after renal biopsy. Results: Nuclei with different degrees of DNA fragmentation were mainly found in epithelial cells of tubules, but also in glomerular cells, regardless of the form of GN studied. Transglutaminase II expression was found only in cells with a strong staining for DNA fragmentation. DNA fragmentation localized to glomerular cells was more pronounced in proliferative than in non-proliferative forms of GN, being most abundant in patients with rapid progressive GN. Staining for activated caspase 3 in selected biopsies confirmed the presence of apoptosis. BAX and BCL-2 staining was detected within the same cells, but exhibited a different intracellular distribution. In proliferative GN, the extent of DNA damage in tubular epithelial cells significantly corresponds with the concentration of serum creatinine (p < 0.04) and with urinary excretion of α₁-microglobulin (p < 0.01) at the time of biopsy. A significant correlation (p < 0.01) was seen between glomerular DNA fragmentation and follow-up total proteinuria 12 months after biopsy for proliferative forms of GN. The damaged glomerular area (e.g. mesangial sclerosis) significantly correlated with DNA fragmentation in proliferative, but not in nonproliferative GN at the time of biopsy. Furthermore, glomerular damaged showed a significant correlation with tubular DNA damage in proliferative GN. Conclusion: In glomerular cells, apoptosis may be important for the clearance of proliferating cells whereas in tubules, cell damage showed dependence on the degree of tubular injury mediated by inflammation and/or proteinuria. Although the degree of apoptosis in tubular cells correlates with serum creatinine in proliferative GN at the time of biopsy, it is of limited use to predict future renal function.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

DNA Fragmentation in Chronic Glomerulonephritis: An Immunohistological Analysis

Ott¹,

Aschoff

Pocock³

et al. 2006

Nephron Clin Pract

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“…An alternative approach aimed at detecting nicks in DNA typical for apoptotic chromatin (the TUNEL reaction) has also been applied in lupus studies. The conclusion from these studies is not clear, because the TUNEL reaction has been reported to be positive in several forms of glomerulonephritis, including lupus nephritis (30,(34)(35)(36)(37)(38). The specificity of this method for apoptosis is believed to be rather low, because this reaction may be positive in necrotic, postmortem autolysed, reversibly damaged, or actively transcribed cellular DNA (39).…”

mentioning

confidence: 63%

Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F₁ mice

Zykova¹,

Seredkina²,

Benjaminsen³

et al. 2008

Arthritis & Rheumatism

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Objective. Antinucleosome autoantibodies are pathogenic factors in lupus nephritis. Defects in apoptotic pathways may result in increased levels of apoptotic nucleosomes. The objectives of this study were 1) to determine whether low molecular weight oligonucleosomes are present in the kidneys of autoimmune (NZB ؋ NZW)F 1 mice, 2) to analyze whether the presence of glomerular membrane-associated TUNELpositive electron-dense structures reflect the existence of low molecular weight oligonucleosomes, and 3) to determine an eventual temporal relationship between glomerular electron-dense structures, oligonucleosomes, and proteinuria in these mice.Methods. DNA was isolated from mouse 111s34 hybridoma cells and from the kidneys of normal BALB/c mice in which apoptosis was induced by camptothecin and from the kidneys of (NZB ؋ NZW)F 1 mice at ages 4 weeks, 8 weeks, 20 weeks, and >26 weeks (nephritic mice). The DNA fragmentation pattern was determined with an Agilent bioanalyzer. An electron microscopybased TUNEL assay was performed to detect apoptotic chromatin in glomerular membranes, and immunoelectron microscopy was used to determine antibody binding. Transcription levels for nucleases associated with apoptosis and necrosis were determined by real-time polymerase chain reaction.Results. DNA from camptothecin-treated cell lines and BALB/c mouse kidneys, but not that from untreated (NZB ؋ NZW)F 1 mouse kidneys, demonstrated DNA cleavage consistent with apoptotic fragmentation. DNA from (NZB ؋ NZW)F 1 mice was devoid of apoptotic fragmentation, irrespective of the age of the mice, whereas TUNEL-positive chromatin particles were detected in glomerular membranes in nephritic mice. Renal DNase I transcription was reduced in nephritic mice. Nucleosomal DNA fragmentation in response to camptothecin exposure was highly reduced in (NZB ؋ NZW)F 1 mouse kidneys compared with that in their normal counterparts.Conclusion. The results of this study demonstrate that TUNEL-positive chromatin particles are deposited in the glomeruli of nephritic (NZB ؋ NZW)F 1 mice, due to reduced fragmentation and clearance of chromatin.

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“…Both kidney cell proliferation and apoptosis are possible mechanisms leading to chronic progressive renal histological changes in lupus nephritis [61,62]. Besides inducing proinflammatory cytokines and chemokines, in some studies TWEAK could also affect cell proliferation and survival [24,63].…”

Section: Cell Proliferation and Apoptosismentioning

confidence: 99%

Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis

Liu

Zhou

2012

Inflamm. Res.

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Apoptosis and Proliferating Cell Nuclear Antigen in Lupus Nephritis (Class IV) and Membranoproliferative Glomerulonephritis

Abstract: It can be said that expression of PCNA on renal biopsy was correlated with activity indexes in LN. PCNA may be a prognostic indicator in MPGN and LN. However, apoptosis does not have a predictive value for MPGN and LN.

Cited by 8 publications

References 11 publications

DNA Fragmentation in Chronic Glomerulonephritis: An Immunohistological Analysis

DNA Fragmentation in Chronic Glomerulonephritis: An Immunohistological Analysis

Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F₁ mice

Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis

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Apoptosis and Proliferating Cell Nuclear Antigen in Lupus Nephritis (Class IV) and Membranoproliferative Glomerulonephritis

Abstract: It can be said that expression of PCNA on renal biopsy was correlated with activity indexes in LN. PCNA may be a prognostic indicator in MPGN and LN. However, apoptosis does not have a predictive value for MPGN and LN.

Cited by 8 publications

References 11 publications

DNA Fragmentation in Chronic Glomerulonephritis: An Immunohistological Analysis

DNA Fragmentation in Chronic Glomerulonephritis: An Immunohistological Analysis

Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F1 mice

Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis

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Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F₁ mice