Affinage

LCN2

Neutrophil gelatinase-associated lipocalin · UniProt P80188

Round 2 corrected
Length
198 aa
Mass
22.6 kDa
Annotated
2026-04-28
130 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LCN2 (NGAL/24p3) is a secreted lipocalin that functions as an iron-trafficking protein central to innate immunity, cell survival decisions, and ferroptosis regulation. It captures bacterial siderophores to restrict iron availability during infection and shuttles iron into or out of cells via its receptors SLC22A17 (24p3R) and megalin: iron-loaded LCN2 promotes cell survival, whereas apo-LCN2 induces iron efflux and Bim-dependent apoptosis (PMID:16377555, PMID:15711640, PMID:21507940). LCN2 is transcriptionally activated by NF-κB, C/EBP, Foxo3a, Stat5, and HIF-1α downstream of diverse signals including IL-17, BCR-ABL, EGFR, and TLR4, and is epigenetically regulated by H3K9 β-hydroxybutyrylation and post-translationally targeted for FBXO2-mediated K27-linked ubiquitination and proteasomal degradation (PMID:16798734, PMID:19056725, PMID:40022118, PMID:40791152). Beyond iron sequestration, LCN2 stabilizes MMP-9, promotes epithelial-to-mesenchymal transition through ERα/Slug suppression, attenuates protective autophagy in ischemic cardiomyocytes, drives ferroptosis in cachexia-associated tissues, confers ferroptosis resistance in hepatocellular carcinoma and hepatic stellate cells, and mediates neuroinflammatory injury through astrocytic exosome secretion (PMID:7683678, PMID:19237579, PMID:27800610, PMID:36973755, PMID:34921145, PMID:35440572).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Identification of LCN2 as a lipocalin physically complexed with MMP-9 in neutrophils established the gene product and its first known protein partner, raising the question of what ligand this lipocalin binds and what biological function the NGAL–MMP-9 complex serves.

    Evidence Immunoprecipitation and protein purification from human neutrophils

    PMID:7683678

    Open questions at the time
    • The physiological ligand of the lipocalin pocket was unknown
    • Whether NGAL modulates MMP-9 enzymatic activity or merely stabilizes it was not resolved
    • Function beyond neutrophils was unexplored
  2. 2001 High

    Discovery that secreted 24p3/LCN2 induces apoptosis in hematopoietic cells via an autocrine mechanism linked to a specific cell-surface receptor revealed the protein as a cytokine-like effector of cell death, not merely a structural lipocalin.

    Evidence DNA microarray after IL-3 withdrawal, conditioned medium transfer apoptosis assays in FL5.12 cells

    PMID:11486081

    Open questions at the time
    • The receptor identity was unknown
    • The role of iron in apoptosis induction was not yet established
    • Whether LCN2-mediated apoptosis operates in non-hematopoietic cells was unclear
  3. 2005 High

    Three studies converged to establish LCN2 as a siderophore-dependent iron transporter with two distinct receptors (megalin and 24p3R/SLC22A17) and opposing biological outcomes depending on iron loading: holo-LCN2 delivers iron and promotes survival, while apo-LCN2 depletes intracellular iron and triggers Bim-dependent apoptosis.

    Evidence Surface plasmon resonance for megalin binding; in vivo kidney ischemia-reperfusion rescue with gallium blockade; receptor identification with iron-loaded vs. apo-protein internalization and Bim induction assays

    PMID:15670845 PMID:15711640 PMID:16377555

    Open questions at the time
    • The identity of endogenous mammalian siderophores remained uncertain
    • How 24p3R mediates iron efflux mechanistically was unresolved
    • Whether megalin and 24p3R have tissue-specific or redundant roles was not clarified
  4. 2006 High

    Mapping of the LCN2 promoter identified NF-κB and C/EBP as essential transcriptional drivers downstream of IL-17/TNFα, and subsequent studies placed Foxo3a (repressed by PI3K/Akt) and Stat5 (activated by BCR-ABL) as additional direct regulators, establishing a rich transcriptional control logic linking LCN2 to inflammatory, survival, and oncogenic signaling.

    Evidence Promoter deletion/reporter assays for NF-κB/C/EBP; ChIP for Foxo3a and Stat5 binding; epistasis with constitutively active Akt and BCR-ABL pathway inhibitors

    PMID:16798734 PMID:19056725 PMID:19229297

    Open questions at the time
    • Relative contributions of each transcription factor in different tissues were not quantified
    • Chromatin-level regulation (enhancers, epigenetic marks) was not addressed
    • Post-transcriptional regulation of LCN2 mRNA was unexplored
  5. 2007 High

    NGAL-deficient mice demonstrated that siderophore sequestration confers bacteriostatic innate immunity, while LPS/TLR4 signaling was shown to induce LCN2 via NF-κB in macrophages and C/EBP in epithelial cells, linking pathogen sensing to LCN2 expression.

    Evidence NGAL-KO mice with increased bacterial growth; TLR4-mutant (C3H/HeJ) mice with abrogated LCN2 induction; EMSA for NF-κB and C/EBP

    PMID:17229907 PMID:17490638

    Open questions at the time
    • Contribution of siderophore-independent mechanisms to host defense was not dissected
    • Whether LCN2 targets specific bacterial species preferentially was unclear
  6. 2009 High

    LCN2 was shown to promote epithelial-to-mesenchymal transition in breast cancer by suppressing ERα and inducing Slug, establishing a pro-metastatic role verified by increased invasion and lymph node metastasis in orthotopic models.

    Evidence LCN2 overexpression/silencing with EMT marker analysis, ERα rescue, orthotopic mouse model

    PMID:19237579

    Open questions at the time
    • Whether iron-binding status affects EMT promotion was not tested
    • Relevance to non-breast cancer EMT was not established
    • Direct versus indirect mechanism of ERα suppression was unclear
  7. 2011 High

    24p3-null mice revealed that LCN2-mediated Bim induction is required for normal apoptotic turnover across multiple hematopoietic lineages, confirming in vivo the iron-efflux/Bim axis as a broad physiological cell-death mechanism rather than an in vitro artifact.

    Evidence 24p3-KO mice in two backgrounds with apoptosis assays across neutrophils, mast cells, thymocytes, and erythroid cells; competitive repopulation

    PMID:21507940

    Open questions at the time
    • Whether 24p3R is the sole receptor mediating this effect in vivo was not formally tested
    • Mechanism linking iron depletion to Bim transcription was not defined
  8. 2013 High

    24p3-deficient neutrophils showed impaired chemotaxis, extravasation, and phagocytosis via cytoskeletal gene suppression and microRNA upregulation, revealing a siderophore-independent function of LCN2 in innate immune cell motility.

    Evidence 24p3-KO mice with Listeria/Candida/Staphylococcus infection, neutrophil functional assays, transcriptome and microRNA profiling

    PMID:23543755

    Open questions at the time
    • Which microRNAs are directly regulated by LCN2 was not established
    • Whether the cytoskeletal effect is iron-dependent was untested
  9. 2014 High

    LCN2 was shown to regulate hepatic lipid droplet formation through control of PLIN5 expression, extending its metabolic roles beyond iron trafficking.

    Evidence Lcn2-KO mice on MCD/high-fat diets, adenoviral LCN2 reconstitution restoring PLIN5 and lipid droplets

    PMID:25086218

    Open questions at the time
    • Whether LCN2 regulates PLIN5 transcriptionally or post-transcriptionally was not defined
    • Iron dependence of this lipid-metabolism function was not assessed
  10. 2017 High

    LCN2 was found to suppress protective autophagy in cardiomyocytes during ischemia by inhibiting AMPK/ULK1 signaling and lysosomal function, thereby exacerbating cytochrome c release and apoptosis—a mechanism distinct from its canonical iron-efflux apoptosis pathway.

    Evidence Lcn2-KO mice with coronary ligation, multiple autophagy readouts (LC3, p62, TEM, tandem LC3 assay), DN-Atg5 epistasis

    PMID:27800610

    Open questions at the time
    • How LCN2 inhibits AMPK mechanistically was not resolved
    • Whether this autophagy-suppressive function occurs in other tissues was unknown
  11. 2021 High

    LCN2 was established as a key ferroptosis regulator: NF-κB-driven LCN2 upregulation sequesters iron to confer ferroptosis resistance in hepatocellular carcinoma, while LCN2-neutralizing antibody sensitizes tumors to sorafenib, opening a therapeutic axis.

    Evidence Hepatocyte-specific Lifr-KO mice, NF-κB pathway analysis, ferroptosis assays, LCN2-neutralizing antibody in PDX model

    PMID:34921145

    Open questions at the time
    • Whether LCN2-mediated ferroptosis resistance generalizes beyond HCC was not shown
    • The siderophore identity mediating iron sequestration in cancer was unresolved
  12. 2022 High

    Astrocytic LCN2 was identified as a neuroinflammatory mediator: NHE1–NOX–NF-κB signaling drives LCN2 secretion in exosomes from reactive astrocytes, which induce neuronal death after stroke, establishing a paracrine neurotoxic mechanism.

    Evidence Astrocyte-specific Nhe1-KO mice in stroke model, exosome isolation, NOX/NF-κB inhibitors, neuronal viability assays

    PMID:35440572

    Open questions at the time
    • Whether LCN2 is the sole neurotoxic cargo in astrocytic exosomes was not determined
    • Neuronal receptor mediating exosome-delivered LCN2 toxicity was not identified
  13. 2023 High

    Multiple 2023 studies expanded the ferroptosis/cancer axis: tissue-infiltrating neutrophils were identified as the primary LCN2 source driving ferroptosis-mediated cachexia, LCN2 was shown to bind SLC3A2 to inhibit GSH/GPX4, and LCN2 was found to bind EGFR and enhance its recycling to activate MEK-ERK signaling in oral cancer, while a MafG/MYH9 complex was identified as a novel transcriptional activator via MARE motifs in the LCN2 promoter conferring hepatic stellate cell ferroptosis resistance.

    Evidence Myeloid-specific Lcn2-KO and neutrophil depletion in cachexia models; co-IP of LCN2–SLC3A2; MS-identified LCN2–EGFR interaction with recycling assays and PDX validation; co-IP of MafG–MYH9 with MARE mutagenesis and LCN2 reconstitution in HSCs

    PMID:36899380 PMID:36973755 PMID:37130481 PMID:38871948

    Open questions at the time
    • Whether LCN2–SLC3A2 interaction is direct or requires iron/siderophore was not established
    • EGFR recycling mechanism (trafficking machinery) was not defined
    • MafG/MYH9 role in non-hepatic LCN2 regulation was not tested
  14. 2023 High

    Proteasome inhibition (stabilizing IκBα to suppress NF-κB) and mTOR inhibition (activating autophagic degradation of LCN2) were identified as two mechanistically distinct strategies to reduce astrocytic LCN2 secretion, with the N-terminal signal peptide required for both secretion and pre-secretory autophagic targeting.

    Evidence LPS-stimulated primary astrocytes with bortezomib and mTOR inhibitor, signal peptide deletion mutants, autophagy flux assays, neuronal viability

    PMID:36781380

    Open questions at the time
    • Whether signal peptide-mediated autophagic targeting is unique to LCN2 or generalizable was unknown
    • In vivo validation of these suppressive strategies was not provided
  15. 2024 High

    Two epigenetic/post-translational regulatory layers were defined: H3K9 β-hydroxybutyrylation at the LCN2 promoter activates transcription (repressed by BDH1-mediated ketone rebalancing), and FBXO2 targets LCN2 for K27-linked polyubiquitination and proteasomal degradation, revealing that LCN2 protein levels are tightly controlled by both chromatin and ubiquitin-proteasome pathways.

    Evidence ChIP for H3K9bhb at LCN2 promoter with BDH1-KO/OE and A485 inhibitor; FBXO2–LCN2 co-IP with FBA domain mapping, K27-linkage ubiquitination assay, proteasome inhibitor rescue, FBXO2-KO mice

    PMID:40022118 PMID:40791152

    Open questions at the time
    • Which lysine residues on LCN2 are K27-ubiquitinated was not mapped
    • Whether H3K9bhb regulation of LCN2 occurs in non-cardiac tissues was not tested
    • Interplay between ubiquitination and autophagic degradation of LCN2 was not examined
  16. 2025 Medium

    Post-transcriptional stabilization of LCN2 mRNA by the vault protein MVP (dephosphorylated at S873 by PGAM5) was identified as a mechanism of ferroptosis resistance and sorafenib resistance in HCC, with tenapanor disrupting the MVP–LCN2 mRNA interaction.

    Evidence RBP screening, MVP–LCN2 mRNA binding and stability assays, PGAM5 dephosphorylation at S873, tenapanor treatment in HCC cells and in vivo

    PMID:40262414

    Open questions at the time
    • The RNA element in LCN2 mRNA recognized by MVP was not mapped
    • Independent replication of MVP–LCN2 mRNA axis is needed
    • Whether this mechanism operates outside HCC was not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of endogenous mammalian siderophores that bind LCN2 remains poorly characterized, the structural basis of LCN2's siderophore-independent functions (cytoskeletal regulation, autophagy suppression, EGFR recycling) is largely undefined, and the relative contributions of 24p3R versus megalin in different tissues and disease contexts have not been systematically resolved.
  • Endogenous mammalian siderophore identity remains elusive
  • Structural mechanism for LCN2–EGFR and LCN2–SLC3A2 interactions not resolved at atomic level
  • Tissue-specific receptor usage (24p3R vs. megalin) not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0140104 molecular carrier activity 4 GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 3
Localization
GO:0005576 extracellular region 7 GO:0031410 cytoplasmic vesicle 2 GO:0005811 lipid droplet 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 6 R-HSA-1643685 Disease 5 R-HSA-1430728 Metabolism 4 R-HSA-9612973 Autophagy 2 R-HSA-1474244 Extracellular matrix organization 1
Partners
EGFRFBXO2LOXL2LRP2MMP9MVPSLC22A17SLC3A2
Complex memberships
LCN2-LOXL2-MMP9NGAL-MMP9

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 LCN2 (NGAL) was isolated as a 25-kDa protein physically associated with human neutrophil gelatinase (MMP-9); immunoprecipitation and immunoblotting demonstrated that the 135-kDa form of gelatinase is a complex of 92-kDa gelatinase and NGAL, while the 220-kDa form is a homodimer of gelatinase alone. NGAL was identified as a member of the lipocalin family with one N-glycosylation site. Immunoprecipitation, immunoblotting, protein purification, primary structure determination, N-glycanase treatment The Journal of biological chemistry High 7683678
1991 Mouse 24p3 protein (Lcn2) was identified as a member of the lipocalin protein family based on three conserved sequence motifs, proposing a ligand-binding function for small hydrophobic molecules. Computational sequence analysis using conserved lipocalin motifs Biochemical and biophysical research communications Low 1834059
1997 The human NGAL gene was cloned and sequenced (5869 bp including 1695 bp of 5′ non-transcribed region, seven exons, six introns); transcriptional start sites were identified by RNase protection assay; the promoter contains binding sites for NF-κB, GATA-1, PU.1, and CTF/CBP, consistent with regulation in neutrophils and epithelial cells exposed to microorganisms. Gene cloning, sequencing, RNase protection assay, promoter analysis Genomics High 9339356
2001 LCN2 (24p3) is transcriptionally induced after IL-3 withdrawal in hematopoietic cells; conditioned medium containing secreted 24p3 induces apoptosis in naive IL-3-replete FL5.12 cells via an autocrine pathway; apoptotic sensitivity correlates with presence of a cell-surface receptor for 24p3; 24p3 induces apoptosis across a wide variety of leukocytes but not non-hematopoietic cells. DNA microarray, conditioned medium transfer, apoptosis assays, receptor-binding correlation Science High 11486081
2005 Megalin (LRP2), a member of the LDL receptor family expressed in polarized epithelia, binds NGAL with high affinity (demonstrated by surface plasmon resonance) and mediates its endocytosis in a megalin-antibody-blockable manner in rat yolk sac cells. Surface plasmon resonance, antibody-blocking endocytosis assay in BN16 cells FEBS letters High 15670845
2005 Ngal (LCN2) forms a complex with iron-binding siderophores (Ngal:siderophore:Fe) that is endocytosed by renal proximal tubule cells; this complex upregulates heme oxygenase-1, preserves N-cadherin, and inhibits cell death, protecting the kidney from ischemia-reperfusion injury; iron delivery is required since gallium (siderophore blockade) abolishes rescue; mouse urine contains an endogenous Ngal-dependent siderophore-like activity. Mouse ischemia-reperfusion model, single-dose protein rescue, gallium blockade, immunohistochemistry, in vivo iron delivery assay The Journal of clinical investigation High 15711640
2005 The 24p3 receptor (24p3R) internalizes iron-bound 24p3 to prevent apoptosis by delivering iron to cells, whereas the apo (iron-free) form of 24p3 induces cellular iron efflux and apoptosis through upregulation of the pro-apoptotic protein Bim. Receptor identification, iron-loaded vs. apo-protein internalization assays, Bim induction measurement Cell High 16377555
2007 NGAL exerts bacteriostatic effects by capturing siderophores and depleting them of iron; eukaryotic siderophore-like molecules can bind NGAL to shuttle iron between extracellular and intracellular spaces; NGAL deficiency in mice leads to increased bacterial growth; NGAL acts as a growth and differentiation factor in renal epithelia, with activity enhanced by siderophore:iron complexes. NGAL-deficient mouse model (bacterial growth studies), cell culture differentiation assays, siderophore-binding assays Journal of the American Society of Nephrology High 17229907
2007 LPS-induced endotoxemia increases 24p3/Lcn2 expression in mouse lung and liver within 4 h via TLR-4 signaling; cells from C3H/HeJ mice with a nonfunctional TLR-4 show minimal 24p3 induction; NF-κB nuclear binding activity increases in alveolar macrophages and Type II cells; C/EBP activation occurs only in Type II cells, indicating differential transcription factor usage. In vivo LPS administration, RT-PCR, Western blot, immunohistochemistry, TLR-4 mutant mice, NF-κB and C/EBP EMSA Experimental and molecular pathology Medium 17490638
2008 24p3 is a direct transcriptional target of Foxo3a; PI3K/Akt (but not MAPK) mediates IL-3-repressed 24p3 expression by phosphorylating and inactivating Foxo3a; constitutively active Akt attenuates 24p3 expression and apoptosis after IL-3 withdrawal; Foxo3a binds directly to the 24p3 promoter and induces its activity. Promoter reporter assay, ChIP (Foxo3a binding to 24p3 promoter), constitutively active Akt overexpression, PI3K/MAPK inhibitors, FL5.12 cells The Journal of biological chemistry High 19056725
2009 BCR-ABL upregulates 24p3 expression via the JAK/STAT pathway (Stat5 binds the 24p3 promoter), while simultaneously repressing 24p3R expression by switching Runx3 (activator) to Runx1 (repressor) binding through a Ras signaling pathway; this asymmetry allows BCR-ABL+ cells to secrete apoptosis-inducing 24p3 that kills normal cells expressing 24p3R but not BCR-ABL+ cells themselves; repression of 24p3R is required for imatinib to kill BCR-ABL+ cells. ChIP (Stat5 binding to 24p3 promoter; Runx1/3 binding to 24p3R promoter), signaling pathway inhibitors, imatinib kill assays The EMBO journal High 19229297
2006 IL-17 induces 24p3/lipocalin-2 transcription primarily through two essential promoter elements: NF-κB and C/EBP binding sites; deletion of either site eliminates promoter activity; IL-17 synergizes with TNF-α at the promoter level. NF-κB and C/EBP sites are statistically over-represented in IL-17 target gene promoters. Promoter deletion/reporter assays, TFBS computational analysis across 18 IL-17 target genes The Journal of biological chemistry High 16798734
2009 Lcn2 promotes breast cancer epithelial-to-mesenchymal transition (EMT) by upregulating mesenchymal markers (vimentin, fibronectin), downregulating E-cadherin, and increasing cell motility and invasiveness; this occurs through suppression of ERα and induction of the EMT transcription factor Slug; ERα overexpression reverses Lcn2-induced EMT; in orthotopic models, Lcn2-expressing tumors show increased local invasion and lymph node metastasis. Lcn2 overexpression/silencing in breast cancer cells, EMT marker immunoblotting, motility/invasion assays, ERα rescue, orthotopic mouse model Proceedings of the National Academy of Sciences of the United States of America High 19237579
2010 Lcn2 is an active driver of chronic kidney disease (CKD) progression: Lcn2-/- mice show dramatically reduced renal lesion severity after nephron reduction; Lcn2 expression is induced by EGFR activation; HIF-1α is required for EGFR-induced Lcn2 overexpression; Lcn2 mediates the mitogenic effect of EGFR during renal deterioration (cell proliferation markedly reduced in Lcn2-/- mice); EGFR inhibition prevents Lcn2 upregulation. Lcn2 knockout mice (nephron reduction model), EGFR dominant-negative transgenic mice, HIF-1α requirement assessed, genome-wide expression profiling, EGFR inhibitor treatment The Journal of clinical investigation High 20921623
2011 24p3-null mice accumulate lymphoid, myeloid, and erythroid cells due to apoptotic defects in mature hematopoietic cell types (neutrophils, mast cells, thymocytes, erythroid cells); Bim induction in response to apoptotic stimuli is attenuated in 24p3-/- cells, explaining their resistance to cell death; competitive repopulation shows no enhanced hematopoiesis, confirming a survival rather than proliferation defect. 24p3 null mice (C57BL/6 and 129/SVE backgrounds), competitive repopulation, myelosuppression recovery, apoptosis assays, Bim Western blotting, dexamethasone-induced thymocyte apoptosis The Journal of biological chemistry High 21507940
2012 S2R(Pgrmc1) regulates NGAL/LCN2 expression at the mRNA and protein levels; S2R knockdown decreases MMP-9 activity, and NGAL is required for MMP-9 activity and tumor formation; S2R associates with EGFR to increase EGFR membrane levels, and EGFR/Akt/ERK inhibitors suppress NGAL expression; LCN2 is transcriptionally regulated by NF-κB, and S2R knockdown reduces p65/RelA acetylation and phosphorylation; HDAC1 inhibitors restore p65 acetylation and partially restore NGAL levels. Antibody array screening, siRNA knockdown, RT-PCR, Western blot, gelatin zymography, EGFR/Akt/ERK inhibitors, NF-κB activation assays, HDAC inhibitors The Journal of biological chemistry Medium 22418433
2013 24p3-deficient neutrophils are defective in extravasation to infection sites, chemotaxis, and phagocytosis of bacteria; transcriptome analysis shows selective suppression of genes controlling cytoskeletal reorganization, and microRNAs regulating upstream cytoskeletal proteins are increased in 24p3-/- neutrophils; 24p3-/- mice show enhanced susceptibility to Listeria, Candida, and Staphylococcus, which is not attributable to siderophore sequestration. 24p3-/- mice, in vivo infection models, neutrophil chemotaxis assays, phagocytosis assays, transcriptome analysis, microRNA profiling Journal of immunology High 23543755
2013 The 24p3 receptor (24p3R/SLC22A17) mediates albumin endocytosis in cortical collecting duct cells and activates NF-κB and TGF-β1 signaling in response to luminal albumin, leading to upregulation of profibrotic markers (Snail, vimentin) via an autocrine mechanism. FITC-albumin uptake assay, NF-κB luciferase reporter, NF-κB p65 nuclear translocation, target gene expression, 24p3R siRNA knockdown in mCCDcl1 cells, in vivo PAN nephrotic rat model American journal of physiology. Renal physiology Medium 23884139
2014 LCN2 regulates hepatic lipid droplet formation by controlling expression of the lipid droplet coat protein PLIN5 (Perilipin 5/OXPAT); Lcn2-/- mice fed MCD diet accumulate more hepatic lipids with reduced basal PLIN5; restoration of LCN2 in Lcn2-/- primary hepatocytes by transfection or adenoviral infection restores PLIN5 expression and proper lipid droplet formation. Lcn2-/- mice, MCD and high-fat diet models, adenoviral LCN2 reconstitution, PLIN5 Western blot and IHC, lipid accumulation quantification in vitro and in vivo Biochimica et biophysica acta High 25086218
2017 Glucocorticoids and mineralocorticoids synergize with IL-1 to induce LCN2 expression in chondrogenic cells; this effect requires glucocorticoid or mineralocorticoid receptors and is mediated through PI3K, ERK1/2, and JAK2 kinases. ATDC5 chondrogenic cell line, RT-qPCR, Western blot, signaling pathway inhibitors (PI3K, ERK1/2, JAK2), corticoid receptor antagonists Osteoarthritis and cartilage Medium 28185846
2017 LCN2 attenuates autophagy to exacerbate cardiac apoptosis during ischemia: Lcn2-KO mice show greater ischemia-induced autophagy (LC3/p62 Western blot, LC3 IHC, TEM) and are protected from ischemia-induced caspase-3 activation and cardiac dysfunction; exogenous Lcn2 treatment of cardiomyocytes suppresses autophagic flux (AMPK/ULK1 phosphorylation, tandem RFP/GFP-LC3, cathepsin activity), and exacerbates hypoxia-induced cytochrome c release and caspase-3 activation; autophagy-deficient (dominant-negative Atg5) cells show increased apoptosis with Lcn2 treatment. Lcn2-KO mice (coronary ligation), echocardiography, Western blot (LC3, p62, AMPK, ULK1), TEM, tandem fluorescent LC3 assay, lysosomal cathepsin assay, DN-Atg5 overexpression Journal of cellular physiology High 27800610
2018 Tumor-associated macrophages (TAMs) secrete LCN2 to deliver iron to tumor cells; LCN2-neutralizing antibody restores intracellular iron to pre-TAM levels, establishing LCN2 as an iron transporter between macrophages and tumor cells in the microenvironment. TAM co-culture, LCN2 ELISA, intracellular iron measurement, LCN2-neutralizing antibody, tumor cell iron assays International journal of physiology, pathophysiology and pharmacology Medium 29755643
2021 Loss of LIFR in hepatocytes activates NF-κB signaling through SHP1, leading to upregulation of LCN2; LCN2 sequesters iron and confers resistance to ferroptosis inducers; an LCN2-neutralizing antibody enhances ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR/high LCN2. Hepatocyte-specific and inducible Lifr-KO mice, NF-κB pathway analysis, LCN2 expression measurement, ferroptosis assays (lipid peroxidation, cell death), LCN2-neutralizing antibody in PDX tumor model Nature communications High 34921145
2022 NOX (NADPH oxidase)-NF-κB signaling in reactive astrocytes drives LCN2 expression and secretion after stroke; astrocyte-specific NHE1 deletion reduces astrogliosis and LCN2/GFAP expression, decreasing neuronal loss; ischemia triggers LCN2-containing exosome secretion from astrocytes that causes neuronal death; NHE1 inhibitor (HOE642) reduces LCN2+ exosome secretion; LCN2-mediated neuronal apoptosis and neurite degeneration are attenuated by NHE1 inhibition. Astrocyte-specific Nhe1 conditional KO mice (stroke model), in vitro ischemia in astrocyte cultures, exosome isolation and characterization, Western blot, NOX/NF-κB inhibitors, neuronal viability assays Cell death & disease High 35440572
2022 Glioma-derived exosomes upregulate LCN2 in brain microvascular endothelial cells via the JAK-STAT3 pathway (LCN2 is not delivered from exosomes but induced in recipient cells); LCN2 upregulation increases membrane fluidity of endothelial cells, facilitating nanocapsule crossing of the blood-brain barrier; LCN2 knockdown in endothelial cells abrogates the exosome-induced membrane fluidity effect. Tandem mass tag proteomics, JAK-STAT3 pathway inhibitors, LCN2 siRNA knockdown, membrane fluidity assay, in vivo nanocapsule BBB crossing (IP and IV injection) Journal of controlled release Medium 35341902
2023 LCN2 secretion from reactive astrocytes can be reduced by two mechanisms: (1) proteasome inhibition suppresses NF-κB activation through IκBα stabilization, downregulating Lcn2 expression; (2) autophagic flux activation via mTOR inhibition degrades intracellular LCN2 pre-secretorily; the N-terminal signal peptide of LCN2 is critical for both its secretion and pre-secretory autophagic degradation; reducing secreted LCN2 by either mechanism increases neuronal viability under inflammatory stress. LPS-stimulated primary astrocytes, proteasome inhibitor (bortezomib), mTOR inhibitor, IκBα Western blot, autophagy flux assays (LC3/SQSTM1), LCN2 signal peptide deletion mutants, neuronal viability assays in conditioned medium Autophagy High 36781380
2023 Tissue-infiltrating neutrophils (TI-Neu) are the primary source of LCN2 in lung cancer cachexia; LCN2 secreted by TI-Neu induces ferroptosis in adipose and muscle tissues, causing wasting; antibody depletion of TI-Neu and myeloid-specific Lcn2 knockout both prevent ferroptosis and tissue wasting; chemical inhibition of ferroptosis alleviates tissue wasting and prolongs survival. Lung cancer mouse models, LCN2 blockade/overexpression, antibody depletion of neutrophils, myeloid-specific Lcn2 KO (LysM-Cre), ferroptosis inhibitor (ferrostatin), tissue iron/lipid peroxidation assays Journal of hematology & oncology High 36973755
2023 LCN2 binds SLC3A2 (system Xc- heavy chain) and inhibits downstream glutathione synthesis and GPX4 expression, promoting ferroptosis after intracerebral hemorrhage; this interaction was validated by molecular docking and co-immunoprecipitation. Co-immunoprecipitation, molecular docking, proteomics, LCN2 overexpression/rescue experiments, GSH and GPX4 measurement in brain tissue Phytomedicine Medium 37130481
2023 LCN2 binds EGFR and enhances EGFR recycling back to the plasma membrane, thereby activating the EGFR-MEK-ERK cascade in oral squamous cell carcinoma; LCN2 inhibition reduces EGFR phosphorylation and downstream signaling, suppressing proliferation and metastasis. Mass spectrometry, co-IP, immunoblotting, immunofluorescence, EGFR recycling assays, siRNA knockdown, in vivo xenograft and PDX models Journal of experimental & clinical cancer research High 36899380
2023 Increased LCN2 in reactive astrocytes suppresses neurogenesis; anti-neurogenic effects of LCN2 are mediated by SLC22A17 (24p3R); Ngfr expression reduces reactive astrocyte LCN2, and SLC22A17 blockade recapitulates the pro-neurogenic effect; LCN2/SLC22A17 axis downstream of NGFR signaling modulates astrocyte fate in Alzheimer's disease. APP/PS1dE9 mouse model, AAV-Ngfr hippocampal injection, single-cell transcriptomics, spatial proteomics, SLC22A17 functional knockdown, neurogenesis histology, 3D human astroglial cultures NPJ Regenerative medicine Medium 37429840
2023 LCN2 forms a ternary complex with LOXL2 and MMP9; LCN2-LOXL2 and LCN2-MMP9 interactions occur both intracellularly and extracellularly, while LOXL2-MMP9 interaction is only intracellular; the LCN2/LOXL2/MMP9 complex promotes ECM degradation (fibronectin, Matrigel), filopodia formation, microfilament rearrangement via profilin-1 upregulation, and activates FAK/AKT/GSK3β signaling to drive ESCC metastasis. Co-IP (protein-protein interaction assays), co-overexpression, ECM degradation assays, filopodia/actin imaging, SPOCK1 and FAK/AKT/GSK3β pathway Western blots, in vivo tumor growth and metastasis Molecular oncology Medium 37753805
2024 MafG physically interacts with MYH9 (non-muscle myosin heavy chain IIa) and the MafG/MYH9 complex transcriptionally activates LCN2 via a MARE motif in the LCN2 promoter; site-directed mutation of the MARE motif blocks MafG binding and LCN2 transcription; LCN2 re-expression in MafG-knockdown HSCs restores resistance to ferroptosis, thereby promoting liver fibrosis. Co-IP (MafG-MYH9 interaction), MARE motif site-directed mutagenesis, LCN2 promoter reporter assay, LCN2 reconstitution in MafG-KD cells, BDL mouse model, AAV6 HSC-specific MafG knockdown, ferroptosis assays Cell death and differentiation High 38871948
2024 BDH1 overexpression reprograms ketone metabolism, increasing AcAc and decreasing β-OHB, which reduces β-hydroxybutyrylation of H3K9 (H3K9bhb) at the LCN2 promoter, repressing LCN2 transcription; decreased LCN2 in turn weakens NF-κB-RPS3 interaction, reducing NF-κB activity and cardiac injury; LCN2 overexpression reverses BDH1-mediated myocardial protection. BDH1 KO and AAV-BDH1 overexpression in db/db mice, ChIP (H3K9bhb at LCN2 promoter), H3K9bhb inhibitor (A485), NF-κB/RPS3 co-IP, LCN2 overexpression rescue, transcriptome analysis Cardiovascular diabetology High 40022118
2024 FBXO2 binds LCN2 via its FBA domain and promotes K27-linked polyubiquitination of LCN2, driving its proteasomal degradation; FBXO2 co-expression reverses LCN2-induced mitochondrial dysfunction and ferroptosis; LCN2 silencing in FBXO2-deficient mice partially restores disc integrity in intervertebral disc degeneration. Proteomics, co-IP (FBXO2-LCN2 via FBA domain), ubiquitination assay (K27-linked), proteasome inhibitor rescue, LCN2 KD in FBXO2-KO mice, ferroptosis markers Advanced science High 40791152
2025 ROS induces STAT3-mediated MVP transcription; PGAM5 dephosphorylates MVP at S873, enabling MVP to bind LCN2 mRNA and stabilize it, thereby suppressing ferroptosis (reducing lipid peroxidation and intracellular Fe2+) and conferring sorafenib resistance in HCC; disrupting MVP-LCN2 mRNA interaction with tenapanor enhances ferroptosis and sorafenib sensitivity. RBP screening, MVP-LCN2 mRNA binding assay, PGAM5 dephosphorylation assay (S873 phosphorylation site), LCN2 mRNA stability measurement, ferroptosis assays, tenapanor pharmacological inhibition, HCC cell and in vivo models Drug resistance updates Medium 40262414
2013 Computational modeling (B3LYP DFT calculations + protein-ligand docking) demonstrates that NGAL binds Fe(III)-catecholate complexes (mono-, bis-, tris-catecholate) within its lipocalin binding pocket through a network of hydrogen bonds and electrostatic interactions, providing a structural basis for iron-catecholate binding beyond the known enterobactin interaction. B3LYP/6-311G(d,p) quantum calculations, protein-ligand flexible docking, Poisson-Boltzmann electrostatic analysis Journal of molecular graphics & modelling Low 24018130

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2009 Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. American journal of kidney diseases : the official journal of the National Kidney Foundation 982 19850388
1993 Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. The Journal of biological chemistry 978 7683678
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2005 Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. The Journal of clinical investigation 756 15711640
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2007 Dual action of neutrophil gelatinase-associated lipocalin. Journal of the American Society of Nephrology : JASN 596 17229907
2008 Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clinical journal of the American Society of Nephrology : CJASN 579 18337554
2011 The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. Journal of the American College of Cardiology 536 21511111
1997 Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 485 9339356
2008 Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. American journal of kidney diseases : the official journal of the National Kidney Foundation 456 18725016
2011 Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. Journal of the American Society of Nephrology : JASN 449 21836143
2012 The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochimica et biophysica acta 443 22513004
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2009 Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN 428 19176795
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2006 Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 365 16827865
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2007 Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Critical care (London, England) 347 18070344
2017 Lipocalin 2: An Emerging Player in Iron Homeostasis and Inflammation. Annual review of nutrition 336 28628361
2010 Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. The Journal of clinical investigation 320 20921623
2007 NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatric nephrology (Berlin, Germany) 319 17874137
2001 Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science (New York, N.Y.) 311 11486081
2009 Lipocalin 2 promotes breast cancer progression. Proceedings of the National Academy of Sciences of the United States of America 309 19237579
2005 Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Arteriosclerosis, thrombosis, and vascular biology 297 16254208
2005 The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS letters 283 15670845
2011 Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. Journal of the American Society of Nephrology : JASN 281 21836147
2021 A targetable LIFR-NF-κB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis. Nature communications 261 34921145
2014 Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology (Baltimore, Md.) 251 24375576
2006 Identification of common transcriptional regulatory elements in interleukin-17 target genes. The Journal of biological chemistry 250 16798734
2009 NGAL: a biomarker of acute kidney injury and other systemic conditions. International urology and nephrology 168 19582588
2023 The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL). International journal of molecular sciences 153 37445650
1989 SV40-induced expression of mouse gene 24p3 involves a post-transcriptional mechanism. Oncogene 143 2542864
1998 Heterogeneous expression of the lipocalin NGAL in primary breast cancers. International journal of cancer 135 9842963
2018 More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases. Clinical science (London, England : 1979) 107 29739822
1991 Mouse oncogene protein 24p3 is a member of the lipocalin protein family. Biochemical and biophysical research communications 103 1834059
2016 Lipocalin 2 (LCN2) Expression in Hepatic Malfunction and Therapy. Frontiers in physiology 100 27729871
2022 Neutrophil gelatinase-associated lipocalin (NGAL) in kidney injury - A systematic review. Clinica chimica acta; international journal of clinical chemistry 96 36150522
2014 Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer. Oncotarget 96 24742531
2017 The Update of NGAL in Acute Kidney Injury. Current protein & peptide science 92 27634444
2010 From kidney to cardiovascular diseases: NGAL as a biomarker beyond the confines of nephrology. European journal of clinical investigation 82 20415702
2007 Acute endotoxemia is associated with upregulation of lipocalin 24p3/Lcn2 in lung and liver. Experimental and molecular pathology 80 17490638
2015 Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy. Biochimica et biophysica acta 79 26278055
2023 Reduced secretion of LCN2 (lipocalin 2) from reactive astrocytes through autophagic and proteasomal regulation alleviates inflammatory stress and neuronal damage. Autophagy 78 36781380
2023 LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia. Journal of hematology & oncology 73 36973755
2022 NOX activation in reactive astrocytes regulates astrocytic LCN2 expression and neurodegeneration. Cell death & disease 70 35440572
2010 Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus. Endocrine 62 20960272
2013 Impaired neutrophil function in 24p3 null mice contributes to enhanced susceptibility to bacterial infections. Journal of immunology (Baltimore, Md. : 1950) 58 23543755
2013 Albuminuria induces a proinflammatory and profibrotic response in cortical collecting ducts via the 24p3 receptor. American journal of physiology. Renal physiology 54 23884139
2005 24p3 and its receptor: dawn of a new iron age? Cell 53 16377555
2017 Lipocalin-2 (NGAL) Attenuates Autophagy to Exacerbate Cardiac Apoptosis Induced by Myocardial Ischemia. Journal of cellular physiology 52 27800610
2017 Resistin and NGAL are associated with inflammatory response, endothelial activation and clinical outcomes in sepsis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 52 28424824
2009 Lipocalin 2 regulation by thermal stresses: protective role of Lcn2/NGAL against cold and heat stresses. Experimental cell research 50 19732769
2014 Lipocalin-2 (LCN2) regulates PLIN5 expression and intracellular lipid droplet formation in the liver. Biochimica et biophysica acta 49 25086218
1999 Ovarian steroids regulate 24p3 expression in mouse uterus during the natural estrous cycle and the preimplantation period. The Journal of endocrinology 48 10396016
2015 Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer. Cancer prevention research (Philadelphia, Pa.) 46 25591790
2014 KIM-1 and NGAL as biomarkers of nephrotoxicity induced by gentamicin in rats. Molecular and cellular biochemistry 45 25087119
2018 Tumor associated macrophages deliver iron to tumor cells via Lcn2. International journal of physiology, pathophysiology and pharmacology 44 29755643
2022 Glioma-derived exosomes hijack the blood-brain barrier to facilitate nanocapsule delivery via LCN2. Journal of controlled release : official journal of the Controlled Release Society 43 35341902
2014 Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias. Cancers 43 24713998
2018 Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or Sinner? Cancers 42 30231474
2003 Increased expression of the lipocalin 24p3 as an apoptotic mechanism for MK886. The Biochemical journal 40 12614196
2016 Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker. Scientific reports 39 27782193
2009 Neutrophil gelatinase-associated lipocalin (NGAL/Lcn2) is upregulated in gastric mucosa infected with Helicobacter pylori. Virchows Archiv : an international journal of pathology 39 19727808
2009 Transcription and signalling pathways involved in BCR-ABL-mediated misregulation of 24p3 and 24p3R. The EMBO journal 36 19229297
2019 CD4+ T Cell-Derived NGAL Modifies the Outcome of Ischemic Acute Kidney Injury. Journal of immunology (Baltimore, Md. : 1950) 34 31889023
2022 Kdm6a deficiency in microglia/macrophages epigenetically silences Lcn2 expression and reduces photoreceptor dysfunction in diabetic retinopathy. Metabolism: clinical and experimental 33 35995279
2023 Silencing LCN2 suppresses oral squamous cell carcinoma progression by reducing EGFR signal activation and recycling. Journal of experimental & clinical cancer research : CR 32 36899380
2022 Lcn2 mediates adipocyte-muscle-tumor communication and hypothermia in pancreatic cancer cachexia. Molecular metabolism 32 36243318
2018 Expression of neutrophil gelatinase-associated lipocalin (NGAL) in the gut in Crohn's disease. Cell and tissue research 32 29869714
2012 Neutrophil gelatinase-associated lipocalin (NGAL) expression is dependent on the tumor-associated sigma-2 receptor S2RPgrmc1. The Journal of biological chemistry 32 22418433
2010 Neutrophil gelatinase-associated lipocalin (NGAL): a new piece of the anemia puzzle? Medical science monitor : international medical journal of experimental and clinical research 32 20512104
2023 Dihydromyricetin attenuates intracerebral hemorrhage by reversing the effect of LCN2 via the system Xc- pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 31 37130481
2024 MafG/MYH9-LCN2 axis promotes liver fibrosis through inhibiting ferroptosis of hepatic stellate cells. Cell death and differentiation 30 38871948
2018 CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and predict extrathyroidal extension. BMC cancer 30 29321030
2007 Apoptosis induced by uterine 24p3 protein in endometrial carcinoma cell line. Toxicology 29 17420078
2014 Serum and urinary NGAL but not KIM-1 raises in human postrenal AKI. European journal of clinical investigation 27 24837251
2021 TGF-β-induced PLEK2 promotes metastasis and chemoresistance in oesophageal squamous cell carcinoma by regulating LCN2. Cell death & disease 26 34601488
2018 NGAL protects against endotoxin-induced renal tubular cell damage by suppressing apoptosis. BMC nephrology 26 29980183
2025 Regulating astrocyte phenotype by Lcn2 inhibition toward ischemic stroke therapy. Biomaterials 25 39836995
2021 Nerve growth factor orchestrates NGAL and matrix metalloproteinases activity to promote colorectal cancer metastasis. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 24 34255268
2020 LncRNA TMPO-AS1 promotes LCN2 transcriptional activity and exerts oncogenic functions in ovarian cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 32692467
2024 Berberine alleviates neuroinflammation by downregulating NFκB/LCN2 pathway in sepsis-associated encephalopathy: network pharmacology, bioinformatics, and experimental validation. International immunopharmacology 23 38640713
2024 LCN2: Versatile players in breast cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 38171248
2023 A protein complex of LCN2, LOXL2 and MMP9 facilitates tumour metastasis in oesophageal cancer. Molecular oncology 22 37753805
2017 Chronic diazepam administration increases the expression of Lcn2 in the CNS. Pharmacology research & perspectives 22 28596835
2007 Lipocalin 24p3 is regulated by the Wnt pathway independent of regulation by iron. Cancer genetics and cytogenetics 22 17350462
2024 Tumor-secreted LCN2 impairs gastric cancer progression via autocrine inhibition of the 24p3R/JNK/c-Jun/SPARC axis. Cell death & disease 21 39424639
2017 Clinical Relevance of NGAL/MMP-9 Pathway in Patients with Endometrial Cancer. Disease markers 21 29089666
2016 Upregulation of lipocalin-2 (LCN2) in osteoarthritic cartilage is not necessary for cartilage destruction in mice. Osteoarthritis and cartilage 21 27477830
2015 Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and proteinuria predict severity of acute kidney injury in Puumala virus infection. BMC infectious diseases 21 26503619
2023 Nerve growth factor receptor (Ngfr) induces neurogenic plasticity by suppressing reactive astroglial Lcn2/Slc22a17 signaling in Alzheimer's disease. NPJ Regenerative medicine 20 37429840
2018 Validation of an ELISA for detection of neutrophil gelatinase-associated lipocalin (NGAL) in equine serum. Veterinary clinical pathology 20 30403420
2020 Association between neutrophil gelatinase-associated lipocalin (NGAL) and iron profile in chronic renal disease. Archives of physiology and biochemistry 19 31994917
2011 Multiple apoptotic defects in hematopoietic cells from mice lacking lipocalin 24p3. The Journal of biological chemistry 19 21507940
2019 CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors. Cancer medicine 18 31129920
2021 Increased Endocytosis of Cadmium-Metallothionein through the 24p3 Receptor in an In Vivo Model with Reduced Proximal Tubular Activity. International journal of molecular sciences 17 34298880
2017 Corticoids synergize with IL-1 in the induction of LCN2. Osteoarthritis and cartilage 17 28185846
2013 Modeling iron-catecholates binding to NGAL protein. Journal of molecular graphics & modelling 17 24018130
2020 ERα-dependent stimulation of LCN2 in uterine epithelium during mouse early pregnancy. Reproduction (Cambridge, England) 16 31967970
2016 Serum NGAL and copeptin levels as predictors of acute kidney injury in asphyxiated neonates. Clinical and experimental nephrology 16 27590891
2025 LCN2 induces neuronal loss and facilitates sepsis-associated cognitive impairments. Cell death & disease 15 40025014
2024 Lipocalin 2 (LCN2) confers acquired resistance to almonertinib in NSCLC through LCN2-MMP-9 signaling pathway. Pharmacological research 15 38295916
2022 Lipocalin-2 (LCN2) Deficiency Leads to Cellular Changes in Highly Metastatic Human Prostate Cancer Cell Line PC-3. Cells 15 35053376
2021 LCN2 Is a Potential Biomarker for Radioresistance and Recurrence in Nasopharyngeal Carcinoma. Frontiers in oncology 15 33604288
2020 Differential regulation of Lipocalin 2 (LCN2) in doxorubicin-resistant 4T1 triple negative breast cancer cells. Cellular signalling 15 32758668
2016 Interleukin-1β as a driver of renal NGAL production. Cytokine 15 27997859
2010 NGAL immunohistochemical expression in brain primary and metastatic tumors. Clinical neuropathology 15 20860895
2025 BDH1 overexpression alleviates diabetic cardiomyopathy through inhibiting H3K9bhb-mediated transcriptional activation of LCN2. Cardiovascular diabetology 14 40022118
2025 Microglial Lcn2 knockout enhances chronic intracerebral hemorrhage recovery by restoring myelin and reducing inflammation. Theranostics 14 40225581
2025 Faecalibacterium prausnitzii prevents age-related heart failure by suppressing ferroptosis in cardiomyocytes through butyrate-mediated LCN2 regulation. Gut microbes 14 40364435
2024 Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis. Journal of molecular and cellular cardiology 14 38761990
2024 Withaferin A protects against epilepsy by promoting LCN2-mediated astrocyte polarization to stopping neuronal ferroptosis. Phytomedicine : international journal of phytotherapy and phytopharmacology 14 39032282
2019 LCN2-interacting proteins and their expression patterns in brain tumors. Brain research 14 31233712
2015 C-reactive protein but not hepcidin, NGAL and transferrin determines the ESA resistance in hemodialysis patients. Renal failure 14 26539647
2014 NGAL can alternately mediate sunitinib resistance in renal cell carcinoma. The Journal of urology 14 24423438
2011 Both IL-1β and TNF-α regulate NGAL expression in polymorphonuclear granulocytes of chronic hemodialysis patients. Mediators of inflammation 14 21403867
2007 Mouse 24p3 protein has an effect on L929 cell viability. International journal of biological sciences 14 17304338
2025 LCN2 deficiency mitigates the neuroinflammatory damage following acute glaucoma. Theranostics 13 40083945
2008 Identification of 24p3 as a direct target of Foxo3a regulated by interleukin-3 through the phosphoinositide 3-kinase/Akt pathway. The Journal of biological chemistry 13 19056725
2004 The 24p3 gene is induced during involution of the mammary gland and induces apoptosis of mammary epithelial cells. Molecules and cells 13 15055523
2025 MVP-LCN2 axis triggers evasion of ferroptosis to drive hepatocarcinogenesis and sorafenib resistance. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 12 40262414
2025 FBXO2 Alleviates Intervertebral Disc Degeneration via Dual Mechanisms: Activating PINK1-Parkin Mitophagy and Ubiquitinating LCN2 to Suppress Ferroptosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 40791152
2024 G-4 inhibits triple negative breast cancer by inducing cell apoptosis and promoting LCN2-dependent ferroptosis. Biochemical pharmacology 12 38395264
2023 Expression Analysis of Lipocalin 2 (LCN2) in Reproductive and Non-Reproductive Tissues of Esr1-Deficient Mice. International journal of molecular sciences 12 37298232
2003 The lipocalin 24p3, which is an essential molecule in IL-3 withdrawal-induced apoptosis, is not involved in the G-CSF withdrawal-induced apoptosis. European journal of haematology 12 14703690