Earlier studies found lipocalin 2 elevated in complications associated with type 2 diabetes mellitus such as ischemic heart disease. It contains ns0expressed recombinant mouse lipocalin2 and antibodies raised against the recombinant factor. Jul 14, 2017 management of type 2 diabetes mellitus aims to maintain a normal glycemic status, which if not, it may lead to acute andor chronic diabetic complications. Association between increases in urinary neutrophil gelatinaseassociated lipocalin and acute renal dysfunction after. Neutrophil gelatinaseassociated lipocalin ngal is a small circulating protein that is induced in a wide variety of pathological. B are required for lcn2 induction and bind the human lcn2 promoter. Sep 27, 2016 lipocalin 2 lcn2 is a secreted protein that belongs to the lipocalins, a group of transporters of small lipophilic molecules such as steroids, lipopolysaccharides, iron, and fatty acids in circulation. Lipocalin 2 ngal 24p3 plays a role as an ironsequestering protein in the antibacterial innate immune response, and lipocalin 2 deficient mice have increased susceptibility to bacterial infections in the urinary tract. Lipocalin is a family of small molecules transporting extracellular proteins. Increased lcn2 expression has been observed in ovarian. There are numerous experimental and clinical studies available showing that lipocalin 2 lcn2, also known as neutrophil gelatinase.
Suppression of ngal expression causes increased proliferation and decreased apoptosis in imcd cells. Lipocalin 2 is an ironbinding secreted protein that converts embryonic kidney mesenchyme to epithelia. Members of the lipocalin family bind small molecules and cell surface receptors to form macromolecular complexes. The multifaceted roles of neutrophil gelatinase associated. The mechanisms of apical endocytosis and transcytosis of proteins and peptides in the intestine are poorly understood.
Citation mannelqvist, monica, ingunn m stefansson, elisabeth wik. Ngal is involved in innate immunity by sequestrating iron, thus limiting bacterial growth. Lipocalin 2 binds to an iron siderophore that is required for the growth of bacteria. These data characterize lipocalin 2 as an epithelial inducer in ras malignancy and a suppressor of metastasis. Neutrophil gelatinaseassociated lipocalin ngal, 24p3, sip24, lipocalin 2, or siderocalin was originally purified from neutrophils, but with. Lcn2 has been associated with breast cancer progression.
Roles of neutrophil gelatinaseassociated lipocalin ngal in human cancer saverio candido1,2, roberta maestro3, jerry polesel2, alessia catania1, francesca maira1, santo s. Lipocalin 2 can form homodimers and can heterodimerize with the neutrophil gelatinase mmp9. Oct, 2016 lipocalin 2 lcn2, also called neutrophil gelatinase bassociated lipocalin ngal, is an antimicrobial peptide originally identified in neutrophil granules. The lipocalin 2 ngal 24p3 receptor ngal r24p3r is expressed in rodent distal nephron where it mediates protein endocytosis. The present study aimed to compare the diagnostic value of two biomarkers in this regard. In the present diagnostic accuracy study, all children between the ages of 1 month to 14 years were entered. Lipocalin 2 antagonizes the proangiogenic action of ras in. Neutrophil gelatinaseassociated lipocalin suppresses cyst. Urinary neutrophil gelatinaseassociated lipocalin ngal and. Putative ngal ligands, including neutrophil chemotactic agents such as nformylated tripeptides, have all been refuted by recent biochemical and.
The quantikine human lipocalin2ngal immunoassay is a 4. Association of lipocalin2 level, glycemic status and obesity. Lipocalin2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Liver is the major source of elevated serum lipocalin 2 levels after bacterial infection or partial hepatectomy. In the present study, the expression and localization of rodent 24p3r r24p3r and human ngal r hngalr was investigated in intestinal segments. Lipocalin2 lcn2, also known as neutrophil gelatinaseassociated lipocalin ngal, is a secreted glycoprotein that belongs to a group of. Ipr000566 lipocalincytosolic fattyacid binding domain ipr022272 lipocalin family conserved site ipr003087 neutrophil gelatinaseassociated lipocalinepididymalspecific lipocalin12. Heterogeneous expression of the lipocalin ngal in primary breast cancers. Lipocalin 2, an ironsiderophorebinding protein, converts embryonic kidney mesenchyme to epithelia. Lcn2 was discovered nearly 2 decades ago, and its expression in vivo has previously been associated with the acutephase response. First identified as a neutrophil granule component, neutrophil gelatinaseassociated lipocalin ngal. To generate a lipocalin 2expressing adenovirus a pcrderived. Pankaj seth, dale porter, jaana lahtidomenici, yan geng, andrea.
Increased lcn2 levels have been reported in a wide variety of human epithelial cancers, including breast, ovarian, colon, pancreatic, and thyroid 1. Neutrophil gelatinaseassociated lipocalin ngal as a marker of kidney damage davide bolignano, md, valentina donato, md, giuseppe coppolino, md, susanna campo, md, antoine buemi, md, antonio lacquaniti, md, and michele buemi, md neutrophil gelatinaseassociated lipocalin ngal is a protein belonging to the lipocalin superfamily. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Human neutrophil gelatinaseassociated lipocalin ngal. It contains ns0expressed recombinant human lipocalin2 and has been shown to accurately quantitate the recombinant factor. We conclude that ngallipocalin2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus questioning the role of lipocalin2 in cancer development. Lipocalin 2 is an important factor in innate immune responses.
International journal of clinical and experimental neurology, 2 1, 815. Lipocalin2 ngallcn2, a helpme signal in organ inflammation to the editor. Neutrophil gelatinaseassociated lipocalin ngal, 24p3, sip24, lipocalin 2, or siderocalin was originally purified from neutrophils, but with unknown function. Tear lipocalin is a protein belonging to the lipocalin family and the calycine superfamily, which is a diverse set of proteins that function as extracellular binding proteins.
Lipocalin 2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Two decades after its discovery and after a high variety of published findings, lcn2s altered expression has been assigned to critical roles in several pathological organ conditions. There is a controversy regarding accuracy of neutrophil gelatinaseassociated lipocalin ngal and cystatin c in early detection of acute kidney injury aki. Lipocalin 2 in the central nervous system host response to. Analyses of circulating factors were consistent with the observed obesity phenotype in female ferko mice as plasma levels of leptin 2. Human neutrophil gelatinaseassociated lipocalin ngal xpresscard cat. The lipocalin 2ngal24p3 receptor ngalr24p3r is expressed in rodent distal nephron where it mediates protein endocytosis. Neutrophil gelatinaseassociated lipocalin as the real.
The neutrophil lipocalin ngal is a bacteriostatic agent that interferes with siderophoremediated iron acquisition. However, lcn 2 exhibits little homology with human ngal. Expression and function of the lipocalin2 24p3ngal. It is synthesized in renal tubular, intestinal, hepatic, and pulmonary tissue. Lipocalin 2 diminishes invasiveness and metastasis of ras. Lipocalin 2 lcn2 is a 25 kda secretory glycoprotein, also called ngal neutrophil gelatinaseassociated lipocalin. These data characterize lipocalin 2 as an epithelial inducer in ras. No effect of ngallipocalin2 on aggressiveness of cancer. The induction of lipocalin2 expression in vivo and in vitro. Downregulation of epithelial proteins and the induction of mesenchymal proteins emt 1 16 enhance the metastatic potential of epithelial tumors 79, whereas reactivation of epithelial genes reverses the malignant phenotype met. The data collected includes not only links to publications in pubmed, but also provides information about sample types, species, and experimental conditions.
Lipocalin 2 lcn2, or ngal, is a secreted glycoprotein belonging to the lipocalin protein family and was first identified as a gene upregulated in mouse kidney cells infected by sv40 tumor virus. Urinary neutrophil gelatinaseassociated lipocalin ngal. Lipocalin 2 expression is associated with aggressive features of endometrial cancer article begins on next page the harvard community has made this article openly available. Addition of neutrophil gelatinase associated lipocalin ngal, a small secreted protein that binds. Lipocalin 2 deficiency alters estradiol production and. Lipocalin 2 in the pathogenesis of fatty liver disease and nonalcoholic steatohepatitis. In the present study, the expression and localization of rodent 24p3r r24p3r and human ngalr hngalr was investigated in intestinal segments. These lipocalin 2 changes had been linked to obesity and uncontrolled diabetes. Lipocalin2 lcn2 is a member of the secreted lipocalin protein family. Although lipocalins are a broad family of greatly varied proteins, their threedimensional structure is a unifying characteristic. Lipocalin 2 lcn2, also referred to as neutrophil gelatinaseassociated lipocalin or 24p3, is a novel adiposederived cytokine belonging to the lipocalin subfamily of small secreted proteins that bind hydrophobic molecules, including retinoids, fatty acids, and various steroids. Jci lipocalin 2 is essential for chronic kidney disease.
Lcn2 lipocalin 2 acts as bonederived hormone which crosses the bbb and acts on pvn paraventricular nucleus of hypothalamus in the brain. Junichi hanai, tadanori mammoto, pankaj seth, kiyoshi mori, s. Lipocalin2 lcn2 is a member of the family that sequesters ironbound bacterial siderophores. Ngal, 24p3, uterocalin, and neurelated lipocalin, could stimulate the epithelial. In this process, 24p3r in the distal nephron is thought to mediate iron sequestration into epithelia and thereby promote. Despite the low sequence homology around 20%, all lipocalin family members share a com. Neutrophil gelatinaseassociated lipocalin ngal is 25 kda protein of the lipocalin family. The neutrophil lipocalin ngal is a bacteriostatic agent that interferes with. Neutrophil gelatinaseassociated lipocalin suppresses cyst growth. Lipocalin2 lcn2 is a 25 kda secretory glycoprotein, also called ngal neutrophil gelatinaseassociated lipocalin.
Evaluation of neutrophil gelatinase associated lipocalin, as. Lipocalin2 elisa kit rat ngal neutrophil gelatinase. However, it subsequently was shown that many other types of cells, including in the kidney tubule, may. Simple western lane view shows lysates of mouse lung tissue, loaded at 0. The quantikine mouse lipocalin2ngal immunoassay is a 4. Neutrophil gelatinaseassociated lipocalin ngal as a biomarker for acute kidney injury.
Original article neutrophil gelatinaseassociated lipocalin. Lipocalin 2 is a novel regulator of angiogenesis in human. Lipocalin2ngal 24p3, msfi, lcn2 lipocalin2 lcn2 is a 25 kda secretory glycoprotein, also called ngal neutrophil gelatinaseassociated lipocalin. Lcn2 complex cannot be endocytosed into the bacterium, iron starvation ensues, inhibiting continued bacterial growth. Neutrophil gelatinase associated lipocalin is a 25 kda protein and as its name suggests, the protein in neutrophils is often found bound to gelatinaseb also known as matrix metalloproteinase9 1, 2. Neutrophil gelatinaseassociated lipocalin ngal is a protein belonging to the lipocalin superfamily initially found in activated neutrophils, in accordance with its role as an innate antibacterial factor. Lipocalins are proteins that bind and transport various substances. The quantikine human lipocalin2 immunoassay is a 4. Lipocalin 2 is a regulator of macrophage polarization and nf. Lipocalin 2 is also implicated in kidney development and renal injury.
It is expressed in neutrophils and in low levels in the kidney, prostate, and epithelia of the respiratory and alimentary tracts. The wellaccepted function of lcn2 protein is its antibacterial behavior, however, its role in iron regulation, cellular migration, death and morphology modulation have been speculated. Neutrophil gelatinase associated lipocalin ngal also known as migration stimulating factor inhibitor msfi, human neutrophil lipocalin hnl, alpha1 microglobulin related protein, siderocalin or uterocalin is a 198 amino acid glycoprotein encoded by a gene located on the chromosome locus 3p11. This is a pdf file of an unedited manuscript that has. There are numerous experimental and clinical studies available showing that lipocalin 2 lcn2, also known as neutrophil fig. Recombinant human lipocalin2ngal protein, cf 1757lc050. Cellular and molecular targets of estrogen in normal human breast tissue. Reports on lipocalin 2s antimicrobial effects through iron scavenging blockade abound. Xu mj, feng d, wu h, wang h, chan y, kolls j, et al. No effect of ngallipocalin2 on aggressiveness of cancer in. Cellular and molecular targets of estrogen in normal human.
Lcn2 is also a representative gliocalin that is primarily released by glial cells, as well as acts upon them. Lipocalins have an eightstranded, antiparallel, symmetrical. One such transcript is that encoding the protein lipocalin 2 lcn2, also known as neutrophil gelatinaseassociated lipocalin ngal, siderocalin, 24p3, or uterocalin. The mouse homologue of ngal is called lipocalin 2 lcn2. Lipocalin 2 lcn2, commonly referred to as neutrophil gelatinaseassociated lipocalin ngal, is a secreted protein that is a member of the lipocalin protein superfamily. Lipocalin 2 lcn2, also known as neutrophil gelatinaseassociated lipocalin ngal, is a secreted glycoprotein involved in iron trafficking. Kt542 intended use the human lipocalin 2ngal elisa is a highly sensitive twosite enzymelinked immunoassay elisa for the quantitative determination of lipocalin2ngal in human biological samples. The initial functional studies investigated the role of lipocalin 2 lcn 2, the murine homolog of human ngal in a mouse model 1, 14. Lipocalin 2 expression is associated with aggressive features. Evaluation of neutrophil gelatinase associated lipocalin, as a biomarker of renal injury in type 2 diabetic patients mahnoor khan, nakhshab choudhry1, muhammad fahim ul haq3, shahjahan2, sadia mahmood3, sana sarmad, 1 riffat yasmin2 abstract aim.
Dh goetz, ma holmes, n borregaard, me bluhm, kn raymond, rk strong. The quantikine human lipocalin 2ngal immunoassay is a 4. The human lipocalin 2ngal elisa is a highly sensitive twosite enzymelinked immunoassay elisa for the quantitative determination of lipocalin2ngal in human biological samples. Upregulated lipocalin2 in pulmonary hypertension involving. Cowland1, niels borregaard1 1the granulocyte research laboratory, department of hematology, copenhagen. Serum lipocalin 2 levels in acute exercised prediabetic. Wagener g, jan m, kim m, mori k, barasch jm, sladen rn, et al.
Jci lipocalin 2 deactivates macrophages and worsens. Neutrophil gelatinaseassociated lipocalin as the realtime indicator. Lipocalin 2 expression is associated with aggressive. Ngal is involved in innate immunity by sequestrating iron that in turn limits bacterial growth. Circulating ngal is filtered by the glomerulus to be reabsorbed in the proximal tubule. Another steroid hormone demonstrated to regulate ngal expression is estrogen. However, the precise biological roles of ngal are not fully known. Ngal neutrophil gelatinase associated lipocalin aalto. It contains ns0expressed recombinant human lipocalin 2 and has been shown to accurately quantitate the recombinant factor. Pankaj seth, dale porter, jaana lahtidomenici, yan geng, andrea richardson and kornelia polyak. Neutrophil gelatinaseassociated lipocalin ngal as a. One of these genes, lipocalin 2, is a putative in vivo estrogen target gene. Lipocalin 2 binds to ironcontaining enterobactin feent with an extremely high affinity.
Neutrophil gelatinase associated lipocalin ngal, also known as oncogene. Cytokine modulation of lcn2 increases our understanding of gene. Lipocalin 2 ngal 24p3, msfi, lcn2 lipocalin 2 lcn2 is a 25 kda secretory glycoprotein, also called ngal neutrophil gelatinaseassociated lipocalin. Its synthesis is upregulated markedly in tissue injury especially the kidney.
Ngal, 24p3, uterocalin, and neurelated lipocalin, could stimulate the epithelial phenotype. Cellular and molecular targets of estrogen in normal human breast. Roles of neutrophil gelatinaseassociated lipocalin ngal in. Addition of neutrophil gelatinase associated lipocalin ngal, a small secreted protein that binds diverse ligands, to the cells lacking pc1. Neutrophil gelatinaseassociated lipocalin ngal as a marker. In a study analyzing the plasma proteome, lcn2 levels were increased in breast tumorbearing transgenic mice compared to normal littermates and its levels further increased with tumor progression.
Mice lacking lipocalin 2 mouse 24p3 develop normally but show hypersensitivity to bacterial infection. Evaluation of neutrophil gelatinase associated lipocalin. Neutrophil gelatinaseassociated lipocalin as the realtime. Research article open access lipocalin 2 expression is associated with aggressive features of endometrial cancer monica mannelqvist1,2, ingunn m stefansson1,2, elisabeth wik3,4, kanthida kusonmano5, maria b raeder3,4, anne m yan1,6, karlhenning kalland1,6, marsha a moses7,8, helga b salvesen3,4 and lars a akslen1,2 abstract. We found that lipocalin 2 could also convert 4t1rastransformed mesenchymal tumor cells to an epithelial phenotype, increase ecadherin expression, and suppress cell invasiveness in vitro and tumor growth and lung metastases in vivo. Recently, it was identified that ngal activates nephron formation in the embryonic kidney, is rapidly and massively induced in renal failure and possesses kidneyprotective activity. Lipocalin 2 prevents intestinal inflammation by enhancing.
The potential of lipocalin2ngal as biomarker for inflammatory and. Neutrophil gelatinaseassociated lipocalin ngal is a small 25kda molecule that belongs to a superfamily of lipocalins and is normally secreted in low amounts in the lungs, kidneys, trachea, stomach, and colon. Lipocalin 2, also known as neutrophil gelatinaseassociated lipocalin ngal, is a component of granules in neutrophils from tissues that are normally exposed to microorganisms and is upregulated during inflammation. Neutrophil gelatinase associated lipocalin is a 25 kda protein and as its name suggests, the protein in neutrophils is often found bound to gelatinaseb also known as matrix metalloproteinase9 1,2. Lipocalin2 lcn2, also known as oncogene 24p3 or neutrophil gelatinaseassociated lipocalin ngal, is a protein that in humans is encoded by the lcn2 gene. Association of lipocalin2 level, glycemic status and. To evaluate urinary excretion of neutrophil gelatinase associated lipocalin ngal in type 2. Recombinant human lipocalin 2 acts as an antibacterial. Lipocalin 2 lcn2, ngal is a member of the lipocalin superfamily for which a variety of functions have been reported.
Previously, we reported that lipocalin 2 could revert 4t1rastransformed mesenchymal tumor cells to a more epithelial phenotype, increase ecadherin expression, and suppress cell invasiveness in vitro and in vivo, indicating that lipocalin 2 is a metastasis suppressor. Lipocalin 2 deficiency alters estradiol production and estrogen receptor signaling in female mice. Pmc free article guo h, zhang y, brockman da, et al. Novel component of proinflammatory signaling in alzheimers disease article pdf available in the faseb journal 267. Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes joanna m. Lipocalins are a family of low molecular weight proteins 1840 kda with prevalent extracellular functions and in general are proteins with.