Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,3-dihydroxybenzoic acid (2,3-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity; limits bacterial proliferation by sequestering iron bound to microbial siderophores, such as enterobactin. Can also bind siderophores from M.tuberculosis.
Gene References into Functions
LCN2 influences peroxisomal and mitochondrial biology in the liver to maintain triglyceride balance, handle oxidative stress, and control apoptosis.PMID:28396286
High LCN2 expression is associated with stress-induced mitochondrial dysfunction and heart failure.PMID:29378951
Findings of the study revealed that Lcn2 prevents the development of spontaneous colitis in IL-10 deficient mice by enhancing phagocytic bacterial clearance in macrophages. The results clearly demonstrated a crucial role for Lcn2/NGAL in the development of intestinal inflammation by its regulation of mucosal innate immune responses toward enteric commensal bacteria.PMID:27734904
Results suggest that hippocampal LCN2 upregulation might be a potential pathogenic mechanism leading to further disruption of the hippocampus through neurotoxicity and neuroinflammation in vascular dementia (VaD). Astrocytes seem to be the major source of LCN2 in the hippocampus of rodent models and patients of VaD. Control of hippocampal astrocytic LCN2 expression or activity may be important for neuroprotection in VaD.PMID:28581123
Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failurePMID:28615213
the present study used an animal model to identify NGAL as a potential novel biomarker for mechanical-induced lung injury.PMID:28393227
Lipocalin-2 from both myeloid cells and the epithelium combats Klebsiella pneumoniae lung infection in mice.PMID:28396494
Knockout of Lcn2 attenuated tumor-associated lymphangiogenesis and breast tumor metastasisPMID:27353364
Overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in polycystic kidney disease mice, and was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis.PMID:28341240
Either Lcn2 deficiency or anti-Lcn2 antibody blockade limits abdominal aortic aneurysm expansion in mice by decreasing neutrophil infiltration in the aorta.PMID:27229458
Results suggest that blood brain barrier leakage occurs in white matter after subarachnoid hemorrhage (SAH) and that LCN2 contributes to SAH-induced blood brain barrier disruption.PMID:26463936
LCN2 overexpression in bones modifies the bone marrow microenvironment via modulation of the expression of key secreted factors and cytokines, which in turn regulate the hematopoietic stem cell niche behavior enhancing both HSC homing in young mice and erythrocytes production in older mice.PMID:28004388
LCN2 modulated the secretion of proinflammatory cytokines in PSC of the PDAC tumor microenvironment, whereas downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation, and PDAC development.PMID:28249896
results identify lipocalin 2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bonePMID:28273060
Lcn2 can suppress the beneficial cardiac autophagic response to ischemia and that this contributes to enhanced ischemia-induced cell death and cardiac dysfunction.PMID:27800610
Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infectionsPMID:27152948
may potentiate the development of psoriasis via the enhancement of Th17- and antimicrobial peptide-mediated inflammationPMID:26702876
The acute stress protein LCN2, produced from RPE cells and the neural retina, could modulate retinal inflammation and retinal homeostasis; therefore, such families of proteins could contribute to cell survival during retinal insults.PMID:27315541
Stroma-secreted Lcn2 promotes metastasis in vitro and in vivo, thereby contributing to tumor progression.PMID:27038000
study demonstrated a pivotal and causal role of LCN2 in the development of alcoholic fatty liver diseasePMID:27427417
The basic residues Lys-717 and Lys-719 in the C-terminal region of ANK7 contribute to IkappaBzeta binding to the Lcn2 promoter, probably via interaction with the cytosine-rich element required for Lcn2 activation; glutamate substitution for both lysines results in a loss of transcriptionally active complex formation without affecting direct contact of IkappaBzeta with p50.PMID:27489104
The expression of Lcn2 and mPGES-1 is strongly stimulated by lipopolysaccharide (LPS), indicating that Lcn2 mediates LPS-induced inflammation. These findings shed light on the role of Lcn2 during decidualization.PMID:27416888
Dietary curcumin ameliorates western diet-induced atherosclerosis in ApoE-/- mice, which is related to LCN2 down-regulation, anti-hyperlipidemia effect as well as the inhibition of inflammation.PMID:28234242
Urinary L-FABP, NGAL, Kim-1 and albumin levels increased during the acute phase of kidney injury and were significantly correlated with the degree of tubulointerstitial fibrosis during the chronic phase. These markers could detect higher risk of progression to CKD.PMID:27028054
LCN2 drives ethanol-induced neutrophilic inflammation and propagates the development of alcoholic liver disease.PMID:26682726
Lcn2 protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.PMID:27078067
Loss of Lipocalin 2 is associated with Acute Rejection in a Mouse Model of Renal Transplantation.PMID:26595644
Lcn2 KO mice have decreased levels of retinoic acid and retinol in adipose tissue. The protein levels of STRA6 responsible for retinol uptake were significantly decreased in adipose tissue. The retinol transporter RBP4 was increased in adipose tissue but decreased in the circulation, suggesting the impairment of RBP4 secretion in Lcn2 KO adipose tissue.PMID:27008859
The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2PMID:26968114
Thrombin upregulates LCN2 through protease-activated receptor-1 activation and causes brain damage.PMID:26869387
Urine/plasma NGAL expression ratio is a sensitive and specific marker of subclinical acute kidney injury in mice.PMID:26824608
This study demonstrated that up-regulation of miR-138 inhibits the hypoxia-induced cardiomyocyte apoptosis via down-regulating the pro-apoptotic gene expression of Lcn2.PMID:26129883
Data show that albumin induces tubular unfolded protein response via cytosolic calcium rise, which leads to tubular apoptosis by Lipocalin 2 (LCN2) modulation through ATF4PMID:26787103
LCN2 plays a pivotal role in processes involved in atherogenesis by promoting polarization and migration of monocytic cells and development of macrophages towards foam cells.PMID:26367277
Our observations suggest that Lcn2 promotes host resistance to Salmonella Typhimurium infectionPMID:26332507
LCN2 is a neurotoxic factor secreted rapidly in response to cerebral ischaemia.PMID:25702801
PKCdelta phosphorylated LCN2 at T115 and this phosphorylation was reduced in Prkcd (-/-) mice. PKCdelta colocalized with LCN2 in resting and stimulated neutrophils. LCN2 release from neutrophils after cerebral ischemia was reduced in PKCdelta null mice.PMID:25890235
LCN2 is a novel osteoblast mechanoresponding gene.PMID:25112732
Lcn2 expression is highly regulated during cecal ligation and puncture-induced sepsis, suggesting that this antimicrobial protein could have a role as a potential biomarker for the diagnosis of sepsisPMID:25227123
NGAL has a role in inflammation during sepsisPMID:25893429
LCN2, although massively induced in mice after PH, is not relevant in murine hepatic regeneration.PMID:25040147
Increased LCN2 protein levels in the plasma of mice bearing hypoxic tumors suggest Lipocalin2 may be a useful plasma tumor marker.PMID:25467539
Overall, MSCs by innate tropism toward cancer cells can deliver the therapeutic agent, Lcn2, and inhibit cancer metastasisPMID:25740061
These results suggest a role of LCN2 in enhancing brain injury and iron toxicity after ICH.PMID:25853903
neutrophils are the major source of circulating LCN2 in normal and infected conditionsPMID:24599361
Lcn2 loss prevented the NAS-induced increase of PINP, prevented the increase of collagen fibers deposition and collagen I expression in the coronary vessels and the aorta, and blunted the NAS-induced increase in systolic blood pressure.PMID:25987661
Lcn2 is the key secreted factor downstream of Tcf3 that promotes cell migration in vitro and wound healing in vivo.PMID:24909826
an important role of Lcn2 in adipocyte metabolism and inflammationPMID:24818605
amyloid beta toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing Alzheimer's disease.PMID:24853299
Lcn2 plays a role as an anti-inflammatory regulator in macrophage activation via modulating a feed-forward activation of NFkappaB-STAT3 loop.PMID:25127375