Mesangial cell Fas ligand: upregulation in human lupus nephritis and NF-?B-mediated expression in cultured human mesangial cells

Tsukinoki, Tomoko; Sugiyama, Hiroshi; Sunami, Reiko; Kobayashi, Mizuho; Onoda, Tetsuya; Maeshima, Yohei; Yamasaki, Yasushi; Makino, Hírofumi

doi:10.1007/s10157-004-0301-3

Cited by 25 publications

(23 citation statements)

References 28 publications

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“…The regulatory role of NF-jB in apoptosis through the induction of endogenous iNOS has also been documented in other cell types such as gastric epithelial cells in the context of Helicobacter pylori infection [30]. Alternatively, NF-jB may mediate glomerular cell apoptosis through direct induction of proapoptotic target genes encoding TNF-a or FasL [31,32], whereas in tubular cells, NF-jB possibly acts as a survival factor by suppressing TNF-aÀinduced apoptosis, as indicated in a model of mercury exposure [33]. The possibilities are further supported by our observation of increased TNF-a expression in renal tissue of LN [17].…”

Section: Discussionmentioning

confidence: 99%

Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

2006

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Section: Discussionmentioning

confidence: 99%

Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

2006

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“…FasL is normally expressed by renal cells and is upregulated during renal injury [62]. Activation of NF-kappaB upregulates FasL in cultured mesangial cells exposed to inflammatory mediators [63] and in HIV-associated nephropathy podocytes [55]. Fas and FasL are segregated from each other to different cellular compartments in kidney tubular cells: Fas is restricted to the basolateral surface, while FasL is sequestered to an intracellular compartment and, to a lesser extent, the apical surface [64].…”

Section: Fas Ligand: a New Kid In The Blockmentioning

confidence: 99%

“…In vivo, Fas/FasL signaling has been implicated in tubular cell apoptosis in experimental ischemic injury [72], endotoxemia [73], transplant rejection [74], chronic kidney disease [69, 75], tubulointerstitial injury of obstructive uropathy [76], and focal segmental glomerulosclerosis [77, 78]. Apoptosis of glomerular and tubular cells has also been linked to Fas/FasL expression in hypertensive renal disease [79, 80], HIV-associated nephropathy [81], and human proliferative lupus nephritis [63]. This has fueled the search for potential therapeutic applications of Fas targeting.…”

Section: Fas Ligand: a New Kid In The Blockmentioning

confidence: 99%

TNF Superfamily: A Growing Saga of Kidney Injury Modulators

Sanchez-Niño

Benito-Martín

Gonçalves

et al. 2010

Mediators of Inflammation

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Members of the TNF superfamily participate in kidney disease. Tumor necrosis factor (TNF) and Fas ligand regulate renal cell survival and inflammation, and therapeutic targeting improves the outcome of experimental renal injury. TNF-related apoptosis-inducing ligand (TRAIL and its potential decoy receptor osteoprotegerin are the two most upregulated death-related genes in human diabetic nephropathy. TRAIL activates NF-kappaB in tubular cells and promotes apoptosis in tubular cells and podocytes, especially in a high-glucose environment. By contrast, osteoprotegerin plays a protective role against TRAIL-induced apoptosis. Another family member, TNF-like weak inducer of apoptosis (TWEAK induces inflammation and tubular cell death or proliferation, depending on the microenvironment. While TNF only activates canonical NF-kappaB signaling, TWEAK promotes both canonical and noncanonical NF-kappaB activation in tubular cells, regulating different inflammatory responses. TWEAK promotes the secretion of MCP-1 and RANTES through NF-kappaB RelA-containing complexes and upregulates CCl21 and CCL19 expression through NF-kappaB inducing kinase (NIK-) dependent RelB/NF-kappaB2 complexes. In vivo TWEAK promotes postnephrectomy compensatory renal cell proliferation in a noninflammatory milieu. However, in the inflammatory milieu of acute kidney injury, TWEAK promotes tubular cell death and inflammation. Therapeutic targeting of TNF superfamily cytokines, including multipronged approaches targeting several cytokines should be further explored.

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“…Increased expression or activation of apoptosis effector proteins in lupus kidneys has been demonstrated immunohistochemically (12,30), while other studies detected increased expression of both proapoptotic and antiapoptotic proteins (31)(32)(33). An alternative approach aimed at detecting nicks in DNA typical for apoptotic chromatin (the TUNEL reaction) has also been applied in lupus studies.…”

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confidence: 99%

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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Mesangial cell Fas ligand: upregulation in human lupus nephritis and NF-?B-mediated expression in cultured human mesangial cells

Cited by 25 publications

References 28 publications

Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

TNF Superfamily: A Growing Saga of Kidney Injury Modulators

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

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Mesangial cell Fas ligand: upregulation in human lupus nephritis and NF-?B-mediated expression in cultured human mesangial cells

Cited by 25 publications

References 28 publications

Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

Renal cell apoptosis and proliferation may be linked to nuclear factor–κB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis

TNF Superfamily: A Growing Saga of Kidney Injury Modulators

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

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