Affinage

LECT2

Leukocyte cell-derived chemotaxin-2 · UniProt O14960

Length
151 aa
Mass
16.4 kDa
Annotated
2026-06-10
87 papers in source corpus 29 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LECT2 is a liver-derived, 16-kDa secreted protein (hepatokine) that functions as a pleiotropic ligand for cell-surface receptors, transducing metabolic and inflammatory cues into signaling across immune, endothelial, hepatic, and neuronal compartments (PMID:9266841, PMID:24478397). Structurally it adopts an M23 metalloendopeptidase fold that coordinates a single Zn(II) ion but lacks the catalytic histidine and has a substrate groove occluded by an N-terminal loop, rendering it catalytically inactive; it engages the c-Met receptor with micromolar affinity (PMID:27334921). Through the C-type lectin receptor CD209/CD209a it activates macrophages, dendritic cells, and adipocytes via JNK, p38, and NF-κB signaling, modulating phagocytosis and bacterial killing, immune polarization, and inflammation-driven insulin resistance (PMID:23254286, PMID:29650721, PMID:36740832). As a metabolic effector, hepatic LECT2 is repressed by AMPK and impairs insulin signaling in skeletal muscle through JNK, with LECT2 deletion increasing muscle insulin sensitivity (PMID:24478397). On endothelium LECT2 acts as a Tie1 ligand that disrupts Tie1/Tie2 heterodimerization and drives PPAR signaling to inhibit angiogenesis and worsen liver fibrosis, while also binding VEGFR2 to suppress VEGF-driven endothelial proliferation (PMID:27507763, PMID:31474362). It additionally drives haematopoietic stem cell expansion via CD209a, promotes liver regeneration through ADAM10-NOTCH signaling, and regulates hippocampal neurite extension via control of katanin-P60 and microtubule morphology (PMID:27596364, PMID:41811354, PMID:19917270). Hepatic LECT2 transcription is induced by ER stress through ATF4 and by LPS/TLR4-p38-AP-1 signaling (PMID:34808500, PMID:40495481). Loss of bound zinc is obligatory for conversion of LECT2 into amyloid fibrils, a process accelerated by the I40V polymorphism and physiological renal flow shear and underlying ALECT2 amyloidosis (PMID:33617884, PMID:38537700).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 Medium

    Established LECT2 as a novel secreted neutrophil chemotactic factor, defining it as a distinct extracellular signaling protein.

    Evidence Protein purification from PHA-activated T-cell leukemia cells with chemotaxis assay

    PMID:8877413

    Open questions at the time
    • No receptor identified
    • Mechanism of chemotaxis undefined
    • In vitro activity only
  2. 1997 Medium

    Identified the hepatocyte as the principal source of secreted LECT2, framing it as a liver-derived factor.

    Evidence Recombinant expression, ELISA, and immunostaining of human hepatocytes and hepatoma lines

    PMID:9266841

    Open questions at the time
    • Functional consequence of hepatic secretion not addressed
    • Regulation of expression unknown
  3. 1998 Medium

    Defined the gene structure and mapped liver-specific expression to 5' regulatory sequences, anchoring tissue-restricted control.

    Evidence Gene cloning, primer extension, and FISH mapping to chromosome 5q31.1-q32

    PMID:9545637

    Open questions at the time
    • Specific transcription factors not identified
    • No upstream signaling defined
  4. 2003 Medium

    Resolved the disulfide-bonded folded tertiary structure of LECT2, enabling functional recombinant production.

    Evidence Oxidative refolding of E. coli protein with CD/NMR spectroscopy and chemotaxis validation

    PMID:12597887

    Open questions at the time
    • No atomic-resolution fold yet
    • Receptor engagement not structurally mapped
  5. 2012 High

    Identified CD209a as a specific LECT2 receptor on macrophages, establishing a defined receptor-mediated immune function with in vivo protection against sepsis.

    Evidence Receptor binding assay, macrophage phagocytosis/killing assays, and CD209a-macrophage depletion sepsis model

    PMID:23254286

    Open questions at the time
    • Binding interface not structurally defined
    • Intracellular signaling steps not fully resolved at the time
  6. 2014 High

    Cast LECT2 as a hepatokine linking obesity to muscle insulin resistance via AMPK-controlled expression and JNK-dependent signaling.

    Evidence LECT2-KO mice insulin sensitivity, C2C12 JNK phosphorylation, and AMPK manipulation in hepatocytes

    PMID:24478397

    Open questions at the time
    • Muscle receptor mediating the effect not identified
    • Direct receptor on myocytes undefined
  7. 2015 Medium

    Extended CD209/JNK signaling to endothelial and hepatic lipogenic inflammation, mechanistically tying LECT2 to vascular inflammation and lipid accumulation.

    Evidence CD209 siRNA knockdown in HUVEC/THP-1 with JNK readouts and mTOR/SREBP-1 signaling in HepG2 cells

    PMID:26123523 PMID:26297911

    Open questions at the time
    • Direct CD209 binding affinity not measured
    • Cell-type specificity of receptor usage unresolved
  8. 2016 High

    Solved the crystal structure revealing a catalytically dead M23 metalloendopeptidase fold with Zn coordination and demonstrated direct c-Met binding, redefining LECT2 as a receptor ligand rather than a protease.

    Evidence 1.94 Å X-ray crystallography, peptidase assays, and SPR binding to c-Met

    PMID:27334921

    Open questions at the time
    • Functional consequence of c-Met binding not established
    • Role of bound zinc in signaling not addressed
  9. 2016 High

    Demonstrated LECT2/CD209a control of HSC expansion and VEGFR2-mediated angiogenesis suppression, broadening receptor repertoire and physiological roles.

    Evidence In vivo macrophage depletion and TNF-KO HSC experiments; VEGFR2 phosphorylation assays and HCC xenografts

    PMID:27507763 PMID:27596364

    Open questions at the time
    • Direct VEGFR2 binding affinity not quantified
    • Cross-talk among multiple receptors unresolved
  10. 2016 Medium

    Mapped the CD209a intracellular signaling route, identifying a required Ser28 phosphorylation event upstream of Raf-1/NF-κB.

    Evidence Receptor neutralization, phospho-site antibodies, and transfection in fish/macrophage models

    PMID:26876329 PMID:27813598

    Open questions at the time
    • Conservation to mammalian CD209 signaling not fully shown
    • Kinase responsible for Ser28 phosphorylation unidentified
  11. 2019 High

    Identified Tie1 as a LECT2 receptor whose engagement shifts Tie dimerization toward Tie2 homodimers and drives PPAR signaling, mechanistically explaining LECT2-driven fibrosis and sinusoidal capillarization.

    Evidence Binding/co-IP, endothelial functional assays, Lect2-KO rescue, and AAV9-shRNA therapeutic intervention

    PMID:31474362

    Open questions at the time
    • Structural basis of Tie1 engagement undefined
    • Hierarchy among CD209/Tie1/VEGFR2/c-Met engagement unresolved
  12. 2020 Low

    Linked LECT2 downregulation to Wnt/β-catenin-driven osteogenic differentiation of MSCs.

    Evidence LECT2 knockdown in MSCs with Wnt pathway and osteogenic differentiation assays

    PMID:32763823

    Open questions at the time
    • Single method (knockdown) without rescue
    • Receptor mediating the effect not identified
    • No in vivo confirmation
  13. 2021 High

    Established the molecular basis of ALECT2 amyloidosis: zinc loss is obligatory for fibril formation, is pH-dependent, and the I40V mutation destabilizes the zinc-free state.

    Evidence In vitro reconstituted fibril formation with EM, X-ray diffraction, NMR, and zinc-binding measurements

    PMID:33617884

    Open questions at the time
    • Physiological trigger of zinc loss in vivo not defined at the time
    • Fibril atomic structure not yet resolved
  14. 2021 Medium

    Defined LECT2 control of liver macrophage and hepatocyte inflammatory programs, including selective JNK potentiation in Kupffer cells and ER-stress/ATF4-driven hepatic LECT2 induction.

    Evidence LECT2-KO mice, KUP5 signaling dissection, and ATF4 ChIP-qPCR with KD/OE in HepG2 cells

    PMID:33436955 PMID:34808500

    Open questions at the time
    • Receptor mediating Kupffer cell signaling not pinpointed
    • Integration of metabolic and stress inputs incomplete
  15. 2022 Medium

    Showed LECT2-Tie2/Akt/mTOR signaling stabilizes endothelial barriers, demonstrating context-dependent protective endothelial outcomes.

    Evidence Recombinant LECT2 on retinal/HUVEC endothelial cells with permeability and junction protein readouts and intravitreal injection in diabetic mice

    PMID:35262733

    Open questions at the time
    • Reconciliation with anti-angiogenic Tie1 effects unresolved
    • Direct receptor responsible in this context not formally distinguished
  16. 2023 High

    Provided the cryo-EM fibril architecture (ordered core residues 55-75) and showed CD209a-dependent dendritic cell tolerogenic skewing, advancing both the amyloid and immunomodulatory mechanisms.

    Evidence Single-particle cryo-EM of recombinant fibrils; CD209a-KO BMDC assays with T-cell differentiation readouts

    PMID:36740832 PMID:37657439

    Open questions at the time
    • Recombinant fibril core differs from ex-vivo fibrils (later finding)
    • Trigger converting native to fibrillar form in vivo not defined
  17. 2024 Medium

    Demonstrated that physiological renal flow shear, combined with zinc loss, efficiently nucleates LECT2 fibrils and that I40V accelerates this, linking kidney microenvironment to amyloid deposition.

    Evidence Microfluidic shear device with EM and WT vs I40V fibrillation kinetics

    PMID:38537700

    Open questions at the time
    • In vivo confirmation of shear-driven fibrillation lacking
    • Quantitative contribution of shear vs zinc loss not separated
  18. 2025 Medium

    Expanded LECT2 mechanisms to liver regeneration (ADAM10-NOTCH), kidney fibrosis (EGFR/AKT/PI3K), TLR4-p38-AP-1 transcriptional induction, and resolved an ex-vivo patient fibril structure differing from recombinant fibrils.

    Evidence Hepatocyte-specific Lect2-KO with ADAM10 inhibition and co-IP; Lect2-KO kidney fibrosis model; ChIP-qPCR of AP-1 on Lect2 promoter; cryo-EM/MS of patient-derived fibrils (one preprint)

    PMID:40398731 PMID:40495481 PMID:41811354 PMID:bio_10.1101_2025.07.15.664973

    Open questions at the time
    • Receptor mediating ADAM10-NOTCH activation not identified
    • Reconciliation of full-length disulfide-intact ex-vivo fibrils with the recombinant 55-75 core unresolved
    • Kidney fibrosis receptor undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LECT2 selects among its multiple receptors (CD209/CD209a, Tie1, VEGFR2, c-Met) in a given cell type, and what physiological cue triggers in vivo zinc loss and the native-to-amyloid transition, remain unresolved.
  • No structural model of any LECT2-receptor complex
  • Receptor hierarchy/competition mechanism undefined
  • In vivo trigger of pathological fibrillation not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3
Partners
ADAM10CD209KDRMETTEKTIE1

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 LECT2 was purified from culture fluid of PHA-activated human T-cell leukemia SKW-3 cells as a 16-kDa basic protein with neutrophil chemotactic activity, establishing it as a novel chemotactic factor distinct from all previously known chemotactic factors. Protein purification, SDS-PAGE, amino acid sequence analysis, neutrophil chemotaxis assay Immunology letters Medium 8877413
1997 Recombinant LECT2 produced in CHO and L929 cells is a secreted 16-kDa protein expressed in hepatocytes; immunostaining demonstrated diffuse cytoplasmic LECT2 in human hepatocytes, and five of six hepatoma cell lines secreted LECT2 into culture fluids. Stable transfection, recombinant protein production, ELISA, immunostaining with polyclonal and monoclonal antibodies Biochemical and biophysical research communications Medium 9266841
1998 LECT2 is encoded by a ~8 kb gene with four exons and three introns, mapped to human chromosome 5q31.1-q32 by FISH; liver-specific expression is driven by transcriptional control sequences in the 5' untranslated region. Gene cloning, primer extension, fluorescence in situ hybridization (FISH) Genomics Medium 9545637
2003 LECT2 is a 133-amino-acid protein with three intramolecular disulfide bonds; properly refolded recombinant LECT2 from E. coli retains the same tertiary structure as CHO-cell-produced authentic LECT2, confirmed by CD and NMR spectroscopy. Recombinant protein expression and oxidative refolding, CD spectroscopy, NMR spectroscopy, chemotaxis assay Protein expression and purification Medium 12597887
2012 LECT2 activates macrophages (but not polymorphonuclear neutrophils) via the CD209a receptor to enhance phagocytosis, bacterial killing, and gene expression changes; CD209a was identified as a specific binding partner for LECT2 and CD209a-expressing macrophages mediated protection against bacterial sepsis in vivo. Receptor identification by specific interaction assay, in vitro macrophage activation assays (phagocytosis, bacterial killing), in vivo sepsis mouse model with CD209a-expressing macrophage depletion The Journal of experimental medicine High 23254286
2014 LECT2 functions as a hepatokine linking obesity to skeletal muscle insulin resistance: LECT2 expression is negatively regulated by the energy-sensing kinase AMPK in hepatocytes; recombinant LECT2 impairs insulin signaling in C2C12 myocytes via JNK phosphorylation; genetic deletion of LECT2 in mice increases skeletal muscle insulin sensitivity. Recombinant protein treatment of myocytes (Western blot for JNK phosphorylation), LECT2 knockout mice (insulin sensitivity measurement), AMPK manipulation in HepG2/H4IIEC hepatocytes Diabetes High 24478397
2015 LECT2 induces inflammatory responses in human endothelial cells and THP-1 cells via CD209 receptor-mediated JNK phosphorylation, increasing ICAM-1, TNFα, MCP-1, and IL-1β expression and enhancing monocyte adhesion to endothelial cells; CD209 siRNA knockdown abolished these effects. Recombinant LECT2 treatment of HUVECs and THP-1 cells, Western blot, qPCR, siRNA knockdown of CD209, JNK inhibitor experiments, monocyte adhesion assay Metabolism: clinical and experimental Medium 26123523
2015 LECT2 increases mTOR phosphorylation and SREBP-1 cleavage in HepG2 cells via JNK signaling, promoting lipid accumulation and insulin resistance; gemigliptin (DPP-4 inhibitor) reduces LECT2 expression via AMPK-dependent and JNK-dependent mechanisms. Western blot for signaling pathway components in HepG2 cells, LECT2 knockdown, JNK inhibitor and AMPK inhibitor treatments, in vivo high-fat diet mouse model Biochemical pharmacology Medium 26297911
2016 Crystal structure of human LECT2 reveals an M23 metalloendopeptidase fold with conserved Zn(II) coordination but lacking a catalytic histidine residue; the potential substrate-binding groove is blocked by an N-terminal intrachain loop; LECT2 is catalytically inactive as a metalloendopeptidase. Surface plasmon resonance showed LECT2 binds the c-Met receptor with micromolar affinity. X-ray crystallography (1.94 Å resolution), peptidase activity assay against multiple peptide sequences including pentaglycine, surface plasmon resonance (SPR) The Journal of biological chemistry High 27334921
2016 LECT2 drives haematopoietic stem cell (HSC) expansion in bone marrow and mobilization to blood via CD209a receptor; this effect requires macrophages and osteolineage cells and is mediated through reduction of TNF expression in these cells (demonstrated by loss of effect in TNF-KO mice). Recombinant LECT2 administration in mice, HSC quantification by flow cytometry, specific macrophage depletion, TNF knockout mice, CD209a receptor mediation Nature communications High 27596364
2016 LECT2 suppresses VEGF165-induced endothelial cell proliferation, migration, and tube formation by directly binding VEGFR2 and reducing VEGFR2 tyrosine phosphorylation and downstream ERK/AKT phosphorylation, thereby inhibiting angiogenesis in HCC. Recombinant LECT2 treatment of endothelial cells, VEGFR2 phosphorylation assay (Western blot), in vitro angiogenesis assays (proliferation, migration, tube formation), in vivo HCC xenograft model Scientific reports Medium 27507763
2016 LECT2 macrophage activation via a C-type lectin receptor (PaCLR/CD209a homolog in ayu fish) is mediated through NF-κB activation via Raf-1; CD209a Ser28 phosphorylation in the intracellular domain is required for LECT2-induced Raf-1 and NF-κB activation in macrophages. Anti-receptor neutralization, western blot for signaling components, transfection experiments, phosphorylation-site specific antibodies Genetics and molecular research / Fish & shellfish immunology Medium 26876329 27813598
2018 LECT2 promotes inflammation and insulin resistance in adipocytes via a CD209/P38-dependent pathway; LECT2 activates P38 phosphorylation, NF-κB/IκB phosphorylation, and IL-6 expression, impairs insulin signaling (reduced IRS-1 and Akt phosphorylation), reduces glucose uptake, and augments lipid accumulation via SREBP1c. All effects were abrogated by P38 siRNA or CD209 siRNA. Recombinant LECT2 treatment of differentiated 3T3-L1 cells, siRNA knockdown of P38 and CD209, Western blot, glucose uptake assay Journal of molecular endocrinology Medium 29650721
2019 LECT2 is a functional ligand for the endothelial receptor Tie1; LECT2 binding to Tie1 disrupts Tie1/Tie2 heterodimerization, promotes Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits endothelial cell migration and tube formation. In vivo, LECT2 overexpression inhibits portal angiogenesis and promotes sinusoid capillarization, worsening liver fibrosis; Lect2-KO mice showed reversal of these effects; AAV9-LECT2-shRNA treatment attenuated fibrosis. Ligand-receptor binding assay, Co-immunoprecipitation (Tie1/Tie2 dimerization), endothelial cell functional assays (migration, tube formation), Lect2-KO mice, AAV-shRNA in vivo knockdown, PPAR signaling assay Cell High 31474362
2020 Knockdown of LECT2 in MSCs activates the Wnt/β-catenin pathway and promotes osteogenic differentiation; LECT2 expression is decreased during osteogenic differentiation of MSCs, and its downregulation facilitates osteoblast differentiation. LECT2 knockdown in MSCs, Wnt/β-catenin pathway activation assay, osteogenic differentiation assay Biomedicine & pharmacotherapy Low 32763823
2021 Loss of bound zinc (Zn2+) is obligatory for LECT2 fibril formation in vitro; zinc-binding affinity is strongly pH-dependent (9-13% zinc-free under normal blood pH, rising to 80% at pH 6.5). The I40V mutation does not alter zinc-binding affinity but destabilizes the zinc-free conformation. These findings suggest a mechanism where zinc loss combined with I40V mutation promotes ALECT2 amyloidosis. Electron microscopy, X-ray diffraction, NMR, fluorescence spectroscopy, zinc-binding affinity measurements, pH-dependent fibril formation assays The Journal of biological chemistry High 33617884
2021 LECT2 selectively enhances LPS-induced JNK phosphorylation (but not ERK or p38) in Kupffer cells by potentiating upstream MKK4 and TAB2 phosphorylation, shifting liver macrophages to an M1-like phenotype and contributing to NASH-associated liver inflammation. LECT2 KO mice (flow cytometry for M1/M2 macrophage ratios, inflammatory cytokine mRNA), in vitro KUP5 cell signaling (Western blot for JNK, ERK, p38, MKK4, TAB2 phosphorylation), human liver biopsy correlation Scientific reports Medium 33436955
2021 ER stress increases LECT2 expression in hepatocytes via the ATF4 transcription factor; ChIP assay demonstrated ATF4 directly binds three putative binding sites on the LECT2 promoter, and binding is promoted by ER stress inducers. ATF4 knockdown suppressed ER stress-induced LECT2 expression; ATF4 overexpression enhanced it. ER stress induction in HepG2 cells, siRNA knockdown of UPR pathway genes, ATF4 overexpression, ChIP-qPCR assay, in vivo obese mouse liver expression analysis Biochemical and biophysical research communications Medium 34808500
2022 LECT2 ameliorates hyperglycemia-induced blood-retinal barrier impairment by activating the Tie2/Akt/mTOR signaling pathway, increasing interendothelial tight junction proteins (ZO1, VE-cadherin, occludin) and attenuating endothelial cell permeability, migration, and tube formation. Recombinant LECT2 treatment of HRMECs and HUVECs under high-glucose conditions, Western blot for Tie2/Akt/mTOR pathway and junction proteins, FITC-dextran permeability assay, intravitreal injection in streptozotocin-induced diabetic mice, electron microscopy Investigative ophthalmology & visual science Medium 35262733
2023 Cryo-EM structure of recombinant human LECT2 amyloid fibrils reveals two mating protofilaments with ordered core spanning residues 55-75 of the LECT2 sequence; the fibril core is stabilized by hydrophobic contacts and hydrogen-bonded uncharged polar residues, and fibrils are resistant to 3M urea and proteinase K. Single-particle cryo-EM, protease/denaturant resistance assays Structure High 37657439
2023 LECT2 modulates dendritic cell function during H. pylori infection via CD209a receptor; LECT2 promoted BMDC maturation and skewed cytokine production toward IL-10 (anti-inflammatory) and away from IL-23p40, shifting T-cell differentiation from Th1/Th17 toward Treg. CD209a-deficient BMDCs did not respond to LECT2. The signaling pathway involves CD209a-JNK/P38 MAPK. LECT2 treatment of bone marrow-derived DCs from WT, CD209a-KO, and LECT2-KO mice; flow cytometry; Western blot; real-time PCR; T-cell co-culture differentiation assay Journal of gastroenterology and hepatology Medium 36740832
2024 Physiological kidney-like flow shear (generated by microfluidic device with progressively narrowing channels) efficiently induces LECT2 fibril formation in combination with zinc loss; the I40V mutation accelerates fibril formation and increases aggregate size and density under flow shear conditions. Fibril morphology differs between laminar flow shear and shaking/stirring. Microfluidic device mimicking renal flow shear, electron microscopy of resulting fibrils, comparison of WT vs I40V LECT2 fibrillation kinetics The Journal of biological chemistry Medium 38537700
2025 LECT2 promotes liver regeneration by activating the ADAM10-NOTCH signaling pathway; hepatocyte-specific Lect2-KO impairs liver regeneration after partial hepatectomy across multiple age groups, and ADAM10 suppression abolishes the pro-regenerative effect of LECT2 overexpression. AAV-mediated Lect2 overexpression enhanced post-hepatectomy regenerative capacity. RNA-seq, scRNA-seq, hepatocyte-specific Lect2-KO mice, co-immunoprecipitation, ADAM10 inhibition experiments, AAV-mediated Lect2 overexpression, Ki-67/PCNA staining Hepatology communications Medium 41811354
2025 LPS directly induces LECT2 expression in hepatocytes via TLR4 receptor signaling; downstream p38 MAPK activates AP-1 (c-Fos/c-Jun), which directly binds a putative AP-1-like site on the Lect2 promoter as confirmed by ChIP-qPCR, driving LECT2 transcription during inflammation. TLR4-specific inhibitor, p38 MAPK inhibitor/agonist, c-Fos/c-Jun overexpression, ChIP-qPCR, Lect2 promoter analysis in AML12 hepatocytes BMB reports Medium 40495481
2025 Ex-vivo ALECT2 amyloid fibrils extracted from a patient kidney show structural polymorphism: a predominant single-protofilament morphology comprising full-length 133-residue LECT2 retaining all three native disulfide bonds, and two minor double-protofilament morphologies with similar fold but different inter-filament interfaces. Mass spectrometry revealed acetylation within fibrils. Cryo-EM of ex-vivo patient-derived fibrils, mass spectrometry bioRxiv (preprint)preprint Medium bio_10.1101_2025.07.15.664973
2009 LECT2 regulates axon and dendrite extension in hippocampal neurons; neurons from LECT2-KO mice showed significantly shorter axons and dendrites than wild-type, and displayed altered expression of neurotrophins NGF, BDNF, and NT-3 during neuronal development. LECT2-KO mouse hippocampal neuron culture, morphometric analysis of neurite extension, neurotrophin expression analysis Brain research Medium 19917270
2010 LECT2 regulates neuritic extension through control of microtubule morphology by modulating katanin-P60 levels; LECT2-KO hippocampal neurons showed fragmented, shorter microtubules and elevated katanin-P60 expression compared to wild-type neurons. LECT2-KO mouse hippocampal neuron culture, microtubule morphology analysis, Western blot for katanin-P60 expression Neuroreport Low 20463617
2025 LECT2 overexpression in endothelial cells promotes kidney fibrosis via activation of the EGFR/AKT/PI3K pathway; Lect2-KO mice showed reduced fibrosis, reduced myofibroblast activation, and less collagen deposition in a kidney fibrosis model, with increased CHOP expression and earlier endothelial cell activation. Lect2-KO mice kidney fibrosis model, LECT2 overexpression in EA.hy926 cells, Western blot for EGFR/AKT/PI3K pathway, histological analysis, Lect2 reporter mice Life sciences Medium 40398731

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis. Cell 184 31474362
1996 Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2. Immunology letters 162 8877413
2014 LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance. Diabetes 127 24478397
2012 LECT2 protects mice against bacterial sepsis by activating macrophages via the CD209a receptor. The Journal of experimental medicine 106 23254286
1998 Molecular cloning of human and bovine LECT2 having a neutrophil chemotactic activity and its specific expression in the liver. Biochimica et biophysica acta 87 9524238
2014 Leukocyte cell-derived chemotaxin 2 (LECT2)-associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States. Blood 68 24415538
2017 Association of leukocyte cell-derived chemotaxin 2 (LECT2) with NAFLD, metabolic syndrome, and atherosclerosis. PloS one 62 28376109
2015 A dipeptidyl peptidase-IV inhibitor improves hepatic steatosis and insulin resistance by AMPK-dependent and JNK-dependent inhibition of LECT2 expression. Biochemical pharmacology 61 26297911
2010 Leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis: a case series. American journal of kidney diseases : the official journal of the National Kidney Foundation 60 20951486
1997 Expression of a neutrophil chemotactic protein LECT2 in human hepatocytes revealed by immunochemical studies using polyclonal and monoclonal antibodies to a recombinant LECT2. Biochemical and biophysical research communications 54 9266841
2015 LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells. Metabolism: clinical and experimental 53 26123523
2021 LECT2 as a hepatokine links liver steatosis to inflammation via activating tissue macrophages in NASH. Scientific reports 48 33436955
2013 Increased serum leukocyte cell-derived chemotaxin 2 (LECT2) levels in obesity and fatty liver. Bioscience trends 48 24390366
2018 LECT2 promotes inflammation and insulin resistance in adipocytes via P38 pathways. Journal of molecular endocrinology 43 29650721
2011 The tumor suppressor function of LECT2 in human hepatocellular carcinoma makes it a potential therapeutic target. Cancer gene therapy 42 21394108
1998 Molecular cloning, structural characterization, and chromosomal mapping of the human LECT2 gene. Genomics 42 9545637
1998 Systemic expression of a newly recognized protein, LECT2, in the human body. Pathology international 42 9832057
2018 Lect2 Controls Inflammatory Monocytes to Constrain the Growth and Progression of Hepatocellular Carcinoma. Hepatology (Baltimore, Md.) 41 30070727
2014 LECT2 improves the outcomes in ayu with Vibrio anguillarum infection via monocytes/macrophages. Fish & shellfish immunology 36 25462453
2016 LECT2 drives haematopoietic stem cell expansion and mobilization via regulating the macrophages and osteolineage cells. Nature communications 35 27596364
2016 Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice. Biochemical and biophysical research communications 33 27562717
2012 Sequencing of the first ayu (Plecoglossus altivelis) macrophage transcriptome and microarray development for investigation the effect of LECT2 on macrophages. Fish & shellfish immunology 32 23257205
2020 Acute Hyperenergetic, High-Fat Feeding Increases Circulating FGF21, LECT2, and Fetuin-A in Healthy Men. The Journal of nutrition 27 31919514
2016 Inhibition of VEGF165/VEGFR2-dependent signaling by LECT2 suppresses hepatocellular carcinoma angiogenesis. Scientific reports 27 27507763
2014 Characterization of the LECT2 gene and its associations with resistance to the big belly disease in Asian seabass. Fish & shellfish immunology 25 24486631
2021 LECT2 Protects Nile Tilapia (Oreochromis niloticus) Against Streptococcus agalatiae Infection. Frontiers in immunology 23 34093564
1998 The mouse Lect2 gene: cloning of cDNA and genomic DNA, structural characterization and chromosomal localization. Gene 23 9714793
1999 Expression pattern of a newly recognized protein, LECT2, in hepatocellular carcinoma and its premalignant lesion. Pathology international 21 10355968
2022 LECT2: A pleiotropic and promising hepatokine, from bench to bedside. Journal of cellular and molecular medicine 20 35656863
2018 Circulating LECT2 levels in newly diagnosed type 2 diabetes mellitus and their association with metabolic parameters: An observational study. Medicine 20 29642178
2017 Characterization of the LECT2 gene and its protective effects against microbial infection via large lymphocytes in Lampetra japonica. Developmental and comparative immunology 20 29056545
2020 Down-regulation of LECT2 promotes osteogenic differentiation of MSCs via activating Wnt/β-catenin pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 32763823
2019 Leukocyte cell derived chemotaxin-2 (Lect2) as a predictor of survival in adult acute liver failure. Translational gastroenterology and hepatology 19 30976720
2016 LECT2 association with macrophage-mediated killing of Helicobacter pylori by activating NF-κB and nitric oxide production. Genetics and molecular research : GMR 19 27813598
2001 Possible changes in expression of chemotaxin LECT2 mRNA in mouse liver after concanavalin A-induced hepatic injury. Biological & pharmaceutical bulletin 19 11305608
2022 LECT2 Ameliorates Blood-Retinal Barrier Impairment Secondary to Diabetes Via Activation of the Tie2/Akt/mTOR Signaling Pathway. Investigative ophthalmology & visual science 18 35262733
2022 LECT2 Is a Novel Antibacterial Protein in Vertebrates. Journal of immunology (Baltimore, Md. : 1950) 18 35365566
2021 Loss of bound zinc facilitates amyloid fibril formation of leukocyte-cell-derived chemotaxin 2 (LECT2). The Journal of biological chemistry 18 33617884
2016 Crystal Structure of Human Leukocyte Cell-derived Chemotaxin 2 (LECT2) Reveals a Mechanistic Basis of Functional Evolution in a Mammalian Protein with an M23 Metalloendopeptidase Fold. The Journal of biological chemistry 18 27334921
2023 β-catenin/TCF4 inhibitors ICG-001 and LF3 alleviate BDL-induced liver fibrosis by suppressing LECT2 signaling. Chemico-biological interactions 17 36639009
2009 Regulation of neurite extension by expression of LECT2 and neurotrophins based on findings in LECT2-knockout mice. Brain research 17 19917270
2021 The molecular structure and role of LECT2 or CHM-II in arthritis, cancer, and other diseases. Journal of cellular physiology 16 34550600
2007 Dynamic change in expression of LECT2 during liver regeneration after partial hepatectomy in mice. Biomedical research (Tokyo, Japan) 16 18000337
2003 Expression, oxidative refolding, and characterization of six-histidine-tagged recombinant human LECT2, a 16-kDa chemotactic protein with three disulfide bonds. Protein expression and purification 16 12597887
2022 Adipose tissue LECT2 expression is associated with obesity and insulin resistance in Korean women. Obesity (Silver Spring, Md.) 15 35722819
2010 Possible role of LECT2 as an intrinsic regulatory factor in SEA-induced toxicity in d-galactosamine-sensitized mice. Clinical immunology (Orlando, Fla.) 15 20805039
2021 LECT-2 amyloidosis: what do we know? Journal of investigative medicine : the official publication of the American Federation for Clinical Research 12 34848562
2016 New Markers in Atherosclerosis: Thrombospondin-2 (THBS-2) and Leukocyte Cell-Derived Chemotaxin-2 (LECT-2); An Immunohistochemical Study. Medical science monitor : international medical journal of experimental and clinical research 12 28039493
2024 Differential analysis of ovarian tissue between high and low-yielded laying hens in the late laying stage and the effect of LECT2 gene on follicular granulosa cells proliferation. Molecular biology reports 11 38300380
2018 Lect2 deficiency is characterised by altered cytokine levels and promotion of intestinal tumourigenesis. Oncotarget 10 30559928
2013 Expression, high-pressure refolding and purification of human leukocyte cell-derived chemotaxin 2 (LECT2). Protein expression and purification 10 23337084
2013 Identification and expression analysis of the leukocyte cell-derived chemotaxin-2 (LECT2) gene in duck (Anas platyrhynchos). Gene 10 24076354
2021 LECT2, A Novel and Direct Biomarker of Liver Fibrosis in Patients With CHB. Frontiers in molecular biosciences 9 34631799
2021 Endoplasmic reticulum stress increases LECT2 expression via ATF4. Biochemical and biophysical research communications 9 34808500
2016 A transmembrane C-type lectin receptor mediates LECT2 effects on head kidney-derived monocytes/macrophages in a teleost, Plecoglossus altivelis. Fish & shellfish immunology 9 26876329
2015 Renal LECT2 amyloidosis: a newly described disorder gaining greater recognition. Clinical nephrology 9 26308079
2024 Loss of LECT2 promotes ovarian cancer progression by inducing cancer invasiveness and facilitating an immunosuppressive environment. Oncogene 8 38177412
2021 Plasma Leukocyte Cell-Derived Chemotaxin 2 (LECT2) as a Risk Factor of Coronary Artery Disease: A Cross-Sectional Study. Angiology 8 34318706
2014 LECT2 makes the amyloid list. Blood 8 24627547
2011 Expressed sequence tags (ESTs) based identification of genes and expression analysis of leukocyte cell-derived chemotaxin-2 (LECT2) from Epinephelus bruneus. Gene 8 21983421
2024 Mimicking kidney flow shear efficiently induces aggregation of LECT2, a protein involved in renal amyloidosis. The Journal of biological chemistry 7 38537700
2020 Genomic and functional characterization of the lect2 gene from Siniperca chuatsi. Fish & shellfish immunology 7 32991992
2024 Antimicrobial Protein LECT2-b Helps Maintain Gut Microbiota Homeostasis via Selectively Targeting Certain Pathogenic Bacteria. Journal of immunology (Baltimore, Md. : 1950) 6 38038392
2024 LECT2 mediates antibacterial immune response induced by Nocardia seriolae infection in the northern snakehead. Fish & shellfish immunology 6 38908810
2023 Cryo-EM structure of a human LECT2 amyloid fibril reveals a network of polar ladders at its core. Structure (London, England : 1993) 6 37657439
2013 Crystallization and preliminary X-ray analysis of human leukocyte cell-derived chemotaxin 2 (LECT2). Acta crystallographica. Section F, Structural biology and crystallization communications 6 23519812
2024 LECT2 Deletion Exacerbates Liver Steatosis and Macrophage Infiltration in a Male Mouse Model of LPS-mediated NASH. Endocrinology 5 38781447
2024 Role of LECT2 in exacerbating atopic dermatitis: insight from in vivo and in vitro models via NF-κB signaling pathway. Frontiers in immunology 5 39206203
2023 Serum Leukocyte Cell-Derived Chemotaxin 2 (LECT2) Level Is Associated with Osteoporosis. Laboratory medicine 5 35976970
2023 LECT2 modulates dendritic cell function after Helicobacter pylori infection via the CD209a receptor. Journal of gastroenterology and hepatology 5 36740832
2018 Effect of a LECT2 on the immune response of peritoneal lecukocytes against Vibrio anguillarum in roughskin sculpin. Fish & shellfish immunology 5 29331349
2012 Cloning, characterization and expression of the LECT2 gene in grass carp. Fish physiology and biochemistry 5 23129417
1997 Preparation of recombinant six-histidine-tagged human LECT2, a chemotactic protein to neutrophils, in Escherichia coli. Cytotechnology 5 22358898
2010 Regulation of katanin-P60 levels by LECT2 adjusts microtubular morphology. Neuroreport 4 20463617
2025 LPS stimulation-induced regulation of LECT2 expression via TLR4 in hepatocytes. BMB reports 1 40495481
2025 LECT2 promotes liver regeneration across developmental stages by activating the ADAM10-NOTCH signaling pathway. Hepatology communications 1 41811354
2023 Cryo-EM Structure of a Human LECT2 Amyloid Fibril Reveals a Network of Polar Ladders at its Core. bioRxiv : the preprint server for biology 1 36798409
2022 Bystander LECT2 amyloidosis in tumor nephrectomy. CEN case reports 1 35986199
2018 Data on functional characterization of LECT2 from Lampetra japonica. Data in brief 1 29845097
2026 ITPR3 promotes liver fibrosis by damaging hepatocytes via the Ca2+/NF-B/LECT2 pathway. Scientific reports 0 41826410
2026 LS21013A-06, a PDE4 inhibitor, preserves blood-brain barrier integrity in experimental ischemic stroke models through PKA-dependent modulation of LECT2. European journal of pharmacology 0 42044766
2026 Hepatic Senp2 deletion resolves the angiogenic switch in fibrosis via β-catenin/LECT2. Biochemical and biophysical research communications 0 42235328
2025 The role of LECT2 in kidney fibrosis progression and endoplasmic reticulum stress. Life sciences 0 40398731
2025 Elevated LECT2 and PEDF in Pediatric MAFLD: Diagnostic Performance and Metabolic Correlations. Diabetes, metabolic syndrome and obesity : targets and therapy 0 41185854
2024 Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia-reperfusion injury. Liver research (Beijing, China) 0 39957753
2023 Mimicking Kidney Flow Shear Efficiently Induces Aggregation of LECT2, a Protein Involved in Renal Amyloidosis. bioRxiv : the preprint server for biology 0 37503176
2013 [Yeast-based production, purification and bioactivity assay of rainbow trout LECT2]. Dong wu xue yan jiu = Zoological research 0 23389976

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