Induction of Neutrophil Gelatinase-Associated Lipocalin in Vascular Injury via Activation of Nuclear Factor-κB

Bu, De-xiu; Hemdahl, Anne-Louise; Gabrielsen, Anders; Fuxe, Jonas; Zhu, Changliang; Eriksson, Per; Yan, Zhenghua

doi:10.2353/ajpath.2006.050706

Cited by 127 publications

(123 citation statements)

References 38 publications

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“…Our data showing that NGAL is secreted in response to IL-1 stimulation, while being absent from normal cartilage (27), indicates that NGAL is a potential biomarker for arthritic disease. In addition, NGAL binds and inhibits the autocatalysis of MMP-9, an interaction cited as a potential therapeutic target in vascular injury, cancer, and arthritis (28)(29)(30). Another strongly IL-1␣-induced protein was CH3L1 (YKL-40), a known target of inflammatory cytokines in human chondrocyte cultures (31).…”

Section: Discussionmentioning

confidence: 99%

Proteomic characterization of mouse cartilage degradation in vitro

Wilson¹,

Belluoccio²,

Little³

et al. 2008

Arthritis & Rheumatism

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Objective.To develop proteomics to analyze mouse cartilage degradation and correlate transcriptional and translational responses to catabolic stimuli.Methods. Proteomic techniques were used to analyze catabolism in mouse femoral head cartilage. Using specific methods to prepare cartilage extracts and conditioned media for 2-dimensional polyacrylamide gel electrophoresis and subsequent tandem mass spectrometry, we identified novel proteins and fragments released into the media of control, interleukin-1␣ (IL-1␣)-treated, and all-trans-retinoic acid (RetA)-treated explants. Fluorescence 2-dimensional difference gel electrophoresis was used to quantify protein expression changes. We also measured changes in messenger RNA (mRNA) expression to distinguish transcriptional and posttranslational regulation of released proteins.Results. Differentially abundant proteins in the media of control and treated explants included fragments of thrombospondin 1 and connective tissue growth factor. IL-1␣ stimulated release of the cartilage degeneration marker matrix metalloproteinase 3, as well as proteins with uncharacterized roles in cartilage pathology, such as neutrophil gelatinase-associated lipocalin. RetA stimulated release of the extracellular matrix proteins cartilage oligomeric matrix protein, link protein, and matrilin-3 into the media, which was accompanied by a dramatic reduction in the corresponding mRNA transcript levels. Gelsolin, which has been implicated in cytoskeletal reorganization in arthritis synovial fibroblasts but has not been previously associated with cartilage pathology, was regulated by IL-1␣ and RetA.Conclusion. In this first analysis of mouse cartilage degradation and protein release using proteomics, we identified proteins and fragments, some of which represent novel candidate biomarkers for cartilage degradation. Applying these proteomic techniques to wild-type and genetically modified mouse cartilage will provide insights into the mechanisms of cartilage degeneration.

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Section: Discussionmentioning

confidence: 99%

Proteomic characterization of mouse cartilage degradation in vitro

Wilson¹,

Belluoccio²,

Little³

et al. 2008

Arthritis & Rheumatism

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“…Lcn2 expression is significantly augmented in patients with coronary heart disease and myocardial infarction (12,21). Plasma Lcn2 was increased after carotid artery injury in rats (22) and in a heterotopic mouse transplanted heart after ischemia/ reperfusion (23).…”

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confidence: 99%

Lipocalin-2 Induces Cardiomyocyte Apoptosis by Increasing Intracellular Iron Accumulation

Ahn

Chang

et al. 2012

Journal of Biological Chemistry

111

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Background:The proinflammatory adipokine lipocalin-2 is associated with obesity-related complications, such as heart failure. Results: Lipocalin-2 induces cardiomyocyte apoptosis via elevating intracellular iron levels and mediates detrimental effects on cardiac function. Conclusion: Lipocalin-2 is an important mediator of cardiac remodeling. Significance: Regulation of cardiomyocyte apoptosis by lipocalin-2, and the mechanistic role of changes in intracellular iron, may contribute to the pathogenesis of obesity-related heart failure.

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“…The expression of NGAL in the liver, macrophages and adipocytes is markedly induced by various pro-inflammatory stimuli through nuclear factor-kB activation. [13][14][15] NGAL was elevated in multiple murine models of obesity, and reduction of NGAL in cultured adipocytes improved insulin sensitivity. Data from db/db mice 16,17 indicated an elevated NGAL expression in the liver, whereas in high-fatfed mice liver NGAL expression tended to be lower.…”

Section: Introductionmentioning

confidence: 99%

Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance

et al. 2009

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Objective: Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations. Design: We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants). Results: Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r ¼ 0.52, Po0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r ¼ 0.36, P ¼ 0.02) and post-load triglyceride concentrations (r ¼ 0.38, P ¼ 0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes. Conclusion: Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.

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Induction of Neutrophil Gelatinase-Associated Lipocalin in Vascular Injury via Activation of Nuclear Factor-κB

Cited by 127 publications

References 38 publications

Proteomic characterization of mouse cartilage degradation in vitro

Proteomic characterization of mouse cartilage degradation in vitro

Lipocalin-2 Induces Cardiomyocyte Apoptosis by Increasing Intracellular Iron Accumulation

Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance

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