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Principles of Clinical Pathology
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Niraj K. Tripathi, Jacqueline M. Tarrant
In the category of urine biomarkers that are LMW, freely filtered, but also upregulated by the kidney during toxicity are NGAL (also known as lipocalin-2) and osteopontin. Basal levels of NGAL in urine likely come from epithelial cells of the thick ascending limb of the loop of Henle and the collecting duct and filtered NGAL should be resorbed by the proximal tubule in states of health (Charlton et al. 2014). NGAL is significantly increased in rat models of tubular injury and showed reversal during recovery of toxicity (Ozer et al. 2010; Sasaki et al. 2011; Tonomura et al. 2010). In dogs, urine NGAL was shown to be an early marker, which corresponded with GFR decline and microscopic grades of severity (Burt et al. 2014; Sasaki et al. 2014; Zhou et al. 2014). Both NGAL and osteopontin can increase during extra-renal inflammation, and similar to LMW markers, can result in higher urine excretion as a consequence of higher serum levels of these biomarkers. Higher urine NGAL and osteopontin were observed in rats with liver toxicity, muscle toxicity, or endotoxemia in the absence of renal toxicity (Vlasakova et al. 2014).
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
This molecule belongs to the lipocalin family of small lipid (and other hydrophobic molecule) binding proteins, which are as ancient as gram-negative bacteria and have only structural conservation but very little sequence homology; thus, it was difficult to discover by genomic searches. The myriad names of lipocalin 2 testify to its multitude of actions. It was called a siderocalin, as it sequesters bacterial siderophores, thus restricting iron supply to bacteria. In the neutrophil granule, it binds to MPO, MMP9 β-galactosidase, and so forth, and is an important component of neutrophil intracellular traps. NGAL might protect proMMP9 from premature activation. Extracellular NGAL is internalized through several receptors, which also triggers several signaling pathways that are not yet fully elucidated. It may act as an intracellular iron metabolism regulator and also has an effect on subcellular localization of transmembrane proteins, such as cadherins and catenins. Several other lipocalins, for example, retinol binding proteins, are also potentially important for angiogenesis in psoriasis. The mother family “calycin,” to which lipocalins belong, also includes fatty acid binding proteins (FABPs), some of which, for example, FABP4 and FABP5, are important in endothelial cell function and psoriasis.
Genitourinary tract
Published in Brian J Pollard, Gareth Kitchen, Handbook of Clinical Anaesthesia, 2017
Brian J Pollard, Gareth Kitchen
The diagnosis of AKI has to date depended on detection of a decrease in kidney function by an increase in serum creatinine concentration which only occurs after a significant decrease in renal function. Earlier detection of AKI would be beneficial. A number of early biomarkers of AKI are currently being investigated. Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein that is bound to neutrophils and expressed in injured epithelial cells in organs including the kidney has emerged as an accurate early biomarker of acute kidney injury. Plasma and urine NGAL have proved sensitive, specific and predictive early biomarkers of AKI after cardiac surgery. Other promising biomarkers are cystatin C, interleukin-18 and kidney injury molecule-1 (KIM-1). Further studies are required to validate the sensitivity and specificity of these biomarkers in clinical samples from large cohorts and from multiple clinical situations. Clinically relevant urinary biomarkers are summarized in Box 5.5.
The Association between Serum Neutrophil Gelatinase-Associated Lipocalin and Depression in Patients with Type 2 Diabetes Mellitus
Published in Experimental Aging Research, 2022
Taihai Wang, Yue Liu, Wenwu Huang
Neutrophil gelatinase-associated lipocalin (NGAL) is acute inflammatory protein with a 25 kDa produced by various cells and is upexpressed by many pro-inflammatory stimuli (Liu & Nilsen-Hamilton, 1995). NGAL can promote apoptosis in neuronal cells and can cause inhibiting neuronal growth due to stress (Mucha et al., 2011; Petrus, Nyakas, & Eiden et al., 2012). Increased circulating NGAL levels have been also found to be associated with chronic inflammatory diseases such as heart failure (HF) and renal insufficiency (Alvelos et al., 2011; Damman, Veldhuisen, Navis, Voors, & Hillege, 2014). One study has suggested that serum levels of NGAL were significantly elevated with clinical severity of new york heart association classification during a follow-up of 2 years and contributed to increased risk of mortality in HF patients (Deursen, Damman, & Voors et al., 2013). Recently, several studies demonstrated that increased serum levels NGAL were independently associated with depressive symptoms, independent of antidepressant used (Naudé et al., 2013). Other inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-ɑ (TNF-ɑ) is previously reported significnat association with depression (Hannestad, Dellagioia, & Bloch, 2011; Vogelzangs et al., 2012). According to previous research background that both type 2 DM and depression are a chronic inflammatory state. Hence, we speculate that NGAL is an interesting inflammatory biomarker to be investigated its serum levels and depressive symptoms in patients with type 2 DM.
Postpartum human breast milk levels of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9)/NGAL complex in normal and pregnancies complicated with insulin-dependent gestational diabetes mellitus. A prospective pilot case-control study
Published in Journal of Obstetrics and Gynaecology, 2020
Dimitra Metallinou, Katerina Lykeridou, Grigorios Karampas, Georgios Theodoros Liosis, Chrysanthi Skevaki, Myrto Rizou, Ioannis Papassotiriou, Demetrios Rizos
The neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, belongs to the superfamily of lipocalins, which are small extracellular proteins, structurally and functionally different in-between (Flower 1996). It is a 25 kDa protein which was first isolated as a complex covalently linked with the 92 kDa matrix metalloproteinase-9 (MMP-9) (Kjeldsen et al. 1993; Kjeldsen et al. 1994; Xu et al. 1994; Goetz et al. 2000). NGAL mRNA is normally expressed in a variety of human tissues, including the uterus, salivary gland, stomach, colon, lung, kidney and the liver, as well as in extracellular fluids such as colostrum, amniotic fluid and cervical mucus (Costantini et al. 2002; Fernandez et al 2005; Makris et al. 2012; Wenyi et al. 2012). Neutrophils, monocytes/macrophages and adipocytes are the cells with abundant NGAL expression. Consequently, NGAL seems to have a crucial role in numerous physiological and pathological pathways including antibacterial activity, embryogenesis, neoplastic growth, renal-cardiovascular disease and epithelium function (Makris et al. 2012).
β2-Microglobulin, Neutrophil Gelatinase-Associated Lipocalin, and Endocan Values in Evaluating Renal Functions in Patients with β-Thalassemia Major
Published in Hemoglobin, 2020
Petek Uzay Cetinkaya, Fatih Mehmet Azik, Volkan Karakus, Bulent Huddam, Nigar Yilmaz
Abnormalities of glomerular filtration rate (GFR) and tubular dysfunction resulting from chronic anemia, hypoxia, iron load and nephrotoxic effects of chelators are seen in β-thal patients [4,5]. Glomerular filtration rate, urea, creatinine, creatinine clearance and serum cystatin C are frequently used to assess glomerular functions; whereas, urine density, pH, and presence of bicarbonate, phosphate, glucose and amino acids in the urine are frequently used to assess tubular functions [6]. Moreover, diagnostic and predictive values of various biomarkers have also been investigated. Among these biomarkers, β2-microglobulin (β2-MG) is a low molecular weight protein used to assess renal tubular functions. β2-Microglobulin is filtered by the glomeruli of normal kidneys, 99.9% of the β2-MG is reabsorbed, and it is excreted in negligible amounts in the urine. Elevated β2-MG level in the urine is the early indicator of proximal tubular damage [7]. Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein and is minimally expressed in many tissues. Its expression increases in situations that lead to epithelial injury. Neutrophil gelatinase-associated lipocalin has a critical role as an indicator of acute renal injury [8]. Endocan is a proteoglycan secreted from the vascular endothelial cells and a marker of endothelial activation. Thus, increased endocan expression is in question in the presence of inflammatory diseases, endothelial pathologies and tumor progression [9].