Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Play a Protective Role Against Rats Ischemia/Reperfusion Renal Injury via Inhibiting Tubular Epithelial Cell Apoptosis

An, Shuxian; Zang, Xiao; Wang, Yuan; Zhuge, Yuzheng; Yu, Qing

doi:10.3109/0886022x.2012.741877

Cited by 25 publications

(22 citation statements)

References 27 publications

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“…In a hypoxia-reperfusion model of renal tubular epithelial cells, NGAL seems to favorably influence the balance of pro-and antiapoptotic factors toward survival (27). Moreover, exogenous NGAL was found to reduce renal tubular cell apoptosis and protect renal function in rats subjected to ischemia-reperfusion injury (28). Thus, sustained increases in circulating NGAL in our patients may represent an active endogenous response improving tubular regeneration and limiting renal injury in these patients.…”

Section: Discussionmentioning

confidence: 82%

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease

Herrmann

Saad

Eirin

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization.Design, setting, participants, & measurements Nonrandomized inpatient studies were performed in patients with unilateral ARAS (.60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R 2 * as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured.Results Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (12.2[21.8 to 10.5] versus 25.3[27.3 to 20.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6619.7 to 36.6619.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R 2 * .30/s: 22.1%620% versus 14.9%618.3%; P,0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=20.65; P,0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P,0.001), and MCP-1 (r=0.96; P,0.001).Conclusions These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines.

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Section: Discussionmentioning

confidence: 82%

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease

Herrmann

Saad

Eirin

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…In addition, some cytokines may directly protect renal tubules. For example, the lipocalin NGAL inhibited the activation of caspase-3 and reduced Bax expression and renal tubular cell apoptosis in ischemic AKI in rats (An et al, 2013). L-FABP (Liver-type fatty acid-binding proteins) attenuated aristolochic acid-induced nephrotoxicity likely through its antioxidant activity in renal tubules (Matsui et al, 2011).…”

Section: Cytokines and Growth Factorsmentioning

confidence: 99%

Renoprotective approaches and strategies in acute kidney injury

Yang

Song

et al. 2016

Pharmacology & Therapeutics

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Acute kidney injury (AKI) is a major renal disease associated with a high mortality rate and increasing prevalence. Decades of research has suggested numerous chemical and biological agents with beneficial effects in AKI. In addition, cell therapy and molecular targeting have been explored for reducing kidney tissue damage and promoting kidney repair or recovery from AKI. Mechanistically, these approaches may mitigate oxidative stress, inflammation, cell death, and mitochondrial and other organellar damage, or activate cytoprotective mechanisms such as autophagy and pro-survival factors. However, none of these findings has been successfully translated into clinical treatment of AKI. In this review, we analyze these findings and propose experimental strategies for the identification of renoprotective agents or methods with clinical potential. Moreover, we propose the consideration of combination therapy by targeting multiple targets in AKI.

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“…The assay for this molecule shows extreme sensitivity but is associated with low specificity [5]. NGAL has become a successful biomarker for functional, toxic, and ischemic renal damage [6] and for cardiorenal syndromes [7], [8]. Concentrations of this small peptide increase in several conditions.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin Increases HLA-G+/FoxP3+ T-Regulatory Cell Population in an In Vitro Model of PBMC

Manna¹,

Ghinatti²,

Tazzari³

et al. 2014

PLoS ONE

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BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is emerging as a mediator of various biological and pathological states. However, the specific biological role of this molecule remains unclear, as it serves as a biomarker for many conditions. The high sensitivity of NGAL as a biomarker coupled with relatively low specificity may hide important biological roles. Data point toward an acute compensatory, protective role for NGAL in response to adverse cellular stresses, including inflammatory and oxidative stress. The aim of this study was to understand whether NGAL modulates the T-cell response through regulation of the human leukocyte antigen G (HLA-G) complex, which is a mediator of tolerance.Methodology/Principal FindingsPeripheral blood mononuclear cells (PBMCs) were obtained from eight healthy donors and isolated by centrifugation on a Ficoll gradient. All donors gave informed consent. PBMCs were treated with four different concentrations of NGAL (40–320 ng/ml) in an iron-loaded or iron-free form. Changes in cell phenotype were analyzed by flow cytometry. NGAL stimulated expression of HLA-G on CD4+ T cells in a dose- and iron-dependent manner. Iron deficiency prevented NGAL-mediated effects, such that HLA-G expression was unaltered. Furthermore, NGAL treatment affected stimulation of regulatory T cells and in vitro expansion of CD4+ CD25+ FoxP3+ cells. An NGAL neutralizing antibody limited HLA-G expression and significantly decreased the percentage of CD4+ CD25+ FoxP3+ cells.Conclusions/SignificanceWe provide in vitro evidence that NGAL is involved in cellular immunity. The potential role of NGAL as an immunomodulatory molecule is based on its ability to induce immune tolerance by upregulating HLA-G expression and expansion of T-regulatory cells in healthy donors. Future studies should further evaluate the role of NGAL in immunology and immunomodulation and its possible relationship to immunosuppressive therapy efficacy, tolerance induction in transplant patients, and other immunological disorders.

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Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Play a Protective Role Against Rats Ischemia/Reperfusion Renal Injury via Inhibiting Tubular Epithelial Cell Apoptosis

Cited by 25 publications

References 27 publications

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease

Renoprotective approaches and strategies in acute kidney injury

Neutrophil Gelatinase-Associated Lipocalin Increases HLA-G+/FoxP3+ T-Regulatory Cell Population in an In Vitro Model of PBMC

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