LCN2 Human
Description
Iron Homeostasis and Innate Immunity
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Binds bacterial siderophores (e.g., enterobactin) to sequester iron, limiting microbial growth .
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Complexes with the mammalian siderophore 2,5-DHBA to regulate intracellular iron levels and prevent oxidative stress .
Cell Signaling and Pathology
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Activates hypertrophic pathways in cardiomyocytes, increasing cell size while reducing proliferation .
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Protects MMP-9 from degradation, enhancing its activity in cancer metastasis and inflammation .
Cancer
LCN2 is overexpressed in epithelial tumors (e.g., breast, colorectal, pancreatic) and promotes:
Cardiovascular Disease
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Elevated plasma LCN2 correlates with cardiac hypertrophy and diastolic dysfunction in type 2 diabetes patients .
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A cis-eQTL (rs13297295) near LCN2 associates with increased cardiac mass in healthy cohorts .
Kidney Injury
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Serves as an early biomarker for acute kidney injury (AKI) due to rapid urinary excretion during proximal tubule damage .
Biomarker Potential
LCN2 is under investigation in 70 clinical trials (as of 2022) for diagnostic and prognostic applications:
Gene Details
| Property | Value |
|---|---|
| Gene ID | 3934 (NCBI) |
| Synonyms | 24p3, NGAL, MSFI, p25 |
| Protein Length | 198 amino acids |
| Chromosomal Location | 9q34.11 |
Tissue Expression
LCN2 is highly expressed in:
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Neutrophils, kidney, prostate, and epithelial linings of the respiratory/alimentary tracts .
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Lower levels in heart muscle and liver under homeostatic conditions .
Receptor Interactions
LCN2 signals through three putative receptors:
Research Gaps and Future Directions
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Mechanistic Insights: The role of LCN2-MMP-9 heterodimers in non-human models remains unclear due to cysteine divergence .
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Therapeutic Targeting: Neutralizing LCN2 in inflammatory diseases (e.g., alcoholic liver disease) shows preclinical promise but requires human trials .
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Developmental Impact: Perinatal LCN2 exposure may reduce cardiomyocyte endowment, predisposing adults to hypertrophy .
Product Specs
Product Science Overview
Lipocalin-2 was initially identified in 1989 through the detection of its messenger RNA, named 24p3, in simian virus 40-infected kidney cells of mouse models. It was first isolated in human neutrophil granules, leading to its name, neutrophil gelatinase-associated lipocalin (NGAL) . The protein is a 25-kDa glycoprotein that is protease-resistant due to its complex formation with matrix metalloprotease-9 (MMP-9) in human neutrophils .
NGAL plays a crucial role in the innate immune response by sequestering iron and preventing its use by bacteria, thus limiting their growth . It binds to bacterial siderophores, which are iron-chelating molecules, and also to the mammalian siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA). This binding ensures that excess free iron does not accumulate in the cytoplasm, preventing the formation of reactive oxygen species .
Upon encountering invading bacteria, toll-like receptors on immune cells stimulate the synthesis and secretion of NGAL. Secreted NGAL then limits bacterial growth by sequestering iron-containing siderophores . Additionally, NGAL functions as a growth factor and participates in synaptic plasticity .
NGAL is used as a biomarker for kidney injury due to its protease resistance and low molecular weight, which allows it to be excreted and detected in urine . Injured epithelial cells in the kidney secrete a monomeric form of NGAL, while activated neutrophils secrete a dimeric form. This distinction can potentially improve acute kidney injury (AKI) diagnostics by differentiating NGAL of inflammatory origin from that of renal origin .
In AKI patients, NGAL levels are elevated in both blood and urine within two hours of injury, and plasma NGAL has been shown to be predictive of dialysis need . NGAL is also associated with chronic kidney disease, contrast-induced nephropathy, kidney transplant, and mortality . Monitoring NGAL levels provides a more precise and sensitive marker for diagnosing AKI compared to serum creatinine levels, reducing delayed diagnosis and treatment .
The therapeutic potential of NGAL is being explored in various clinical trials. Its role in iron regulation and immune response makes it a promising candidate for therapeutic interventions in diseases characterized by iron dysregulation and bacterial infections . Additionally, NGAL’s involvement in cell regulation, proliferation, and differentiation highlights its potential in cancer therapy .
