Elevation of human tumor necrosis factor-like weak inducer of apoptosis in peripheral blood mononuclear cells is correlated with disease activity and lupus nephritis in patients with systemic lupus erythematosus

Liu, Zhichun; Zhou, Qiaoling; Li, Xiaozhao; Yang, Jinghua; Ao, Xiang; Pouranan, Veeraragoo; Zuo, Xiaoxia

doi:10.1016/j.cyto.2010.11.012

Cited by 23 publications

(21 citation statements)

References 27 publications

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“…21,22 Finally, elevated production of TWEAK in lupus PBMCs correlated with disease activity and proteinuria. 23 Thus, both experimental and clinical studies support the hypothesis that TWEAK/Fn14 interactions play an important role in the pathogenesis of antibody-mediated nephritis, including LN. However, the relevant mechanisms have yet to be clarified.…”

mentioning

confidence: 70%

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

Xia

Herlitz

Gindea

et al. 2015

Journal of the American Society of Nephrology

115

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TNF ligand superfamily member 12, also known as TNF-related weak inducer of apoptosis (TWEAK), acts through its receptor, fibroblast growth factor-inducible 14 (Fn14), to mediate several key pathologic processes involved in tissue injury relating to lupus nephritis. To explore the potential for renal protection in lupus nephritis by targeting this pathway, we introduced the Fn14 null allele into the MRL-lpr/lpr lupus mouse strain. At 26-38 weeks of age, female Fn14-knockout MRL-lpr/lpr mice had significantly lower levels of proteinuria compared with female wild-type MRL-lpr/lpr mice. Furthermore, Fn14-knockout mice had significantly improved renal histopathology accompanied by attenuated glomerular and tubulointerstitial inflammation. There was a significant reduction in glomerular Ig deposition in Fn14-knockout mice, despite no detectable differences in either serum levels of antibodies or splenic immune cell subsets. Notably, we found that the Fn14-knockout mice displayed substantial preservation of podocytes in glomeruli and that TWEAK signaling directly damaged barrier function and increased filtration through podocyte and glomerular endothelial cell monolayers. Our results show that deficiency of the Fn14 receptor significantly improves renal disease in a spontaneous lupus nephritis model through prevention of the direct injurious effects of TWEAK on the filtration barrier and/or modulation of cytokine production by resident kidney cells. Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN.

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mentioning

confidence: 70%

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

Xia

Herlitz

Gindea

et al. 2015

Journal of the American Society of Nephrology

115

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“…Liu et al (32) reported that TWEAK expression in the peripheral blood mononuclear cells of patients with LN was significantly higher than that in patients with rheumatoid arthritis and healthy controls. In addition, its elevation was positively correlated with SLEDAI score, anti-double-stranded DNA content and MCP-1 expression, which suggested that TWEAK was associated with LN activity, and that abnormal chemokine levels may also participate in active LN occurrence (32). The present study identified that TWEAK content in the urine of patients with LN was significantly increased compared with that in Figure 2.…”

Section: Discussionmentioning

confidence: 99%

Involvement of TWEAK and the NF-κB signaling pathway in lupus nephritis

Sun

Teng

et al. 2018

Exp Ther Med

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Abstract. Previous findings have identified that tumor necrosis factor-related weak inducer of apoptosis (TWEAK) is associated with lupus nephritis (LN) activity status; however, the mechanism involved remains unclear. The present study aimed to investigate the roles of TWEAK and the nuclear factor (NF)-κB signaling pathway in LN. TWEAK levels in the blood and urine of patients with LN or non-LN systemic lupus erythematosus were measured by ELISA and compared with those in healthy controls. TWEAK expression and NF-κB transcriptional activity in the kidney were detected by western blotting, and Ki-67 and cluster of differentiation (CD) 68 expression were assessed using immunofluorescence. Additionally, human mesangial cells (HMCs) were cultured in vitro and divided into five groups: Normal control, TWEAK stimulus group, TWEAK + TWEAK blocking antibody, TWEAK + NF-κB inhibitor (BAY 11-7082) and TWEAK + combined (blocking antibody + BAY 11-7082). Cell cycle activity and Ki-67 expression in the HMCs were evaluated using flow cytometry, and cell induction of macrophage chemotaxis was determined by a Transwell assay. Levels of the inflammation-associated factors interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1), chemokine ligand 5 (CCL5), IL-8 and IL-10 were also detected by reverse transcription-quantitative polymerase chain reaction. It was observed that the urine levels of TWEAK in patients with LN were significantly elevated compared with those in the other groups (P<0.05). LN kidneys exhibited markedly increased cell proliferative ability, macrophage infiltration, TWEAK expression and NF-κB transcriptional activity compared with normal kidneys. Furthermore, the results indicated that treatment with recombinant TWEAK notably enhanced NF-κB transcriptional activity and significantly promoted cell proliferation and cell cycle activity (P<0.05), induced macrophage chemotaxis (P<0.05), significantly increased the expression of the chemotactic factors IL-6, IL-8, MCP-1 and CCL5 (P<0.05), and significantly reduced anti-inflammatory cytokine IL-10 mRNA expression in HMCs (P<0.05), relative to normal controls. Accordingly, blocking TWEAK function or inhibiting NF-κB activity reversed these effects. Collectively these data indicate that urine TWEAK may be considered as a novel biomarker of LN activity, and that blocking TWEAK function or NF-κB activity may effectively alleviate glomerular mesangial cell proliferation and macrophage chemotaxis.

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“…Potential biomarkers include IL-6 (2), IL-18 (3), MCP-1 (4), VCAM-1 (5, 6), NGAL (7,8), and TWEAK (9,10). Indeed urine may be by far the best source for screening biomarkers for kidney diseases for several reasons.…”

Section: Systemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis

Han

et al. 2013

Molecular & Cellular Proteomics

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There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ϳ280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n ‫؍‬ 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r ‫؍‬ 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. Molecular & Cellular

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Elevation of human tumor necrosis factor-like weak inducer of apoptosis in peripheral blood mononuclear cells is correlated with disease activity and lupus nephritis in patients with systemic lupus erythematosus

Cited by 23 publications

References 27 publications

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

Involvement of TWEAK and the NF-κB signaling pathway in lupus nephritis

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis

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