Affinage

LOX

Protein-lysine 6-oxidase · UniProt P28300

Length
417 aa
Mass
46.9 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

The LOX symbol in this corpus resolves to two distinct proteins whose findings must be read separately: lysyl oxidase (LOX) and the oxidized-LDL scavenger receptor LOX-1 (OLR1). Lysyl oxidase is a copper-dependent amine oxidase that catalyzes covalent cross-linking of collagen and elastin in the extracellular matrix through a quinone cofactor mechanism, with its activity depending on a conserved copper-binding site and lysyl/tyrosyl residues, while its N-terminal propeptide constitutes a functionally separable regulatory module (PMID:12686136). Catalytic-domain mutations (p.Ser280Arg, p.Ser348Arg) lower enzymatic activity, and LOX haploinsufficiency predisposes to thoracic aortic aneurysms and dissections, establishing LOX as a causal determinant of aortic structural integrity (PMID:26838787). The propeptide (LOX-PP) carries a separable tumor-suppressor activity that opposes invasion, an activity abolished by the Arg158Gln variant (PMID:19654310). Beyond ECM cross-linking, LOX is induced by hypoxia and HIF2A to drive fibrotic remodeling and chemoresistance, assembling fibronectin and signaling through ITGA5/FN1/FAK-Src (PMID:32415208, PMID:30388216), and its stiffening of the matrix activates mechanosensitive Piezo1 to trigger GPX4-dependent ferroptosis (PMID:39260063). LOX also acts intracellularly and in the nucleus, transactivating the SNAI2 promoter to drive EMT (PMID:27029493, PMID:25790191), and influences osteoblast differentiation and ROS-mediated RANKL induction in bone (PMID:27606829, PMID:19458888). LOX expression is controlled by inflammatory and miRNA inputs including Th17/IL-17-ERK-AP-1 versus Treg/IL-10-STAT3 signaling and direct repression by miR-30a (PMID:25488748, PMID:32649012). Separately, LOX-1 (OLR1) is a Ca2+-dependent C-type lectin-like scavenger receptor that recognizes oxidized LDL, phosphatidylserine, and activated platelets (PMID:16146427, PMID:11263985), drives endothelial and macrophage atherogenic signaling via MAP kinase activation, NLRP3 inflammasome activation, and foam-cell formation (PMID:24776598, PMID:11735125), and is regulated by ADAM10/SPPL2-mediated proteolysis, HRD1-dependent ubiquitination, and let-7g/miR-98 (PMID:30819724, PMID:32308114, PMID:22135361, PMID:29549823).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 Medium

    Established that LOX-1 (OLR1) scavenger receptor expression is differentially controlled relative to other modified-LDL receptors, framing it as a regulated determinant of macrophage lipid uptake.

    Evidence TGF-β1 treatment of THP-1 and primary human monocytes, RT-PCR and flow cytometry comparing CD36, SR-A and LOX-1

    PMID:10749696

    Open questions at the time
    • Does not establish functional consequence for atherogenesis in vivo
    • Mechanism of differential transcriptional control not defined
  2. 2001 Medium

    Linked LOX-1 activation to a definable signaling output, placing ox-LDL→LOX-1→MAP kinase→eNOS suppression as an endothelial dysfunction axis and identifying platelet-borne LOX-1 as activation-dependent.

    Evidence Human coronary endothelial cells ± statins with eNOS/MAPK readouts; platelet RT-PCR, flow cytometry, and antibody blocking of ox-LDL binding

    PMID:11263985 PMID:11735125

    Open questions at the time
    • Single cell type for endothelial signaling
    • Direct receptor-effector coupling not reconstituted
  3. 2003 Medium

    Defined the enzymatic and domain architecture of lysyl oxidase and showed transcriptional and ischemic induction of LOX-1, distinguishing the two proteins' biology.

    Evidence Domain/sequence analysis and BMP-1 processing for LOX; EMSA of NF-κB on LOX-1 promoter under high glucose; rat ischemia-reperfusion with anti-LOX-1 antibody

    PMID:12507499 PMID:12686136 PMID:12829655

    Open questions at the time
    • LOX copper/quinone mechanism not reconstituted by full mutagenesis
    • LOX-1 cardiomyocyte mechanism limited to single model
  4. 2009 High

    Separated the LOX propeptide tumor-suppressor function from catalytic activity and revealed an intracellular role for LOX in osteoblast differentiation beyond ECM cross-linking.

    Evidence Arg158Gln LOX-PP variant in xenograft and invasion assays; Lox(-/-) primary calvarial osteoblasts with differentiation and DNA-synthesis readouts

    PMID:19458888 PMID:19654310

    Open questions at the time
    • Molecular target of LOX-PP tumor suppression not identified
    • Mechanism of intracellular LOX action in osteoblasts undefined
  5. 2011 High

    Identified post-transcriptional control of LOX-1 by let-7g and its upstream OCT-1/PKC circuit, showing how ox-LDL feeds forward to sustain receptor expression.

    Evidence 3'-UTR luciferase reporter, OCT-1 ChIP and promoter assay, let-7g mimics/inhibitors with Ca2+/PKC inhibitors

    PMID:22135361

    Open questions at the time
    • In vivo relevance of the let-7g/OCT-1 loop not tested
    • Single regulatory cell context
  6. 2014 High

    Expanded the mechanistic reach of both proteins: LOX-1 to macrophage ROS→mtDNA damage→autophagy→NLRP3 inflammasome inflammation, and LOX to ROS-driven RANKL induction, nuclear localization in glioblastoma invasion, and miR-30a repression.

    Evidence LOX-1 siRNA/antibody with DNase II knockdown and NLRP3 assays; RANKL/RANK KO osteoclastogenesis; BAPN/siRNA in glioblastoma with localization IHC; miR-30a mimics in thyroid cancer models

    PMID:24776598 PMID:25488748 PMID:25790191 PMID:27606829

    Open questions at the time
    • Nuclear import mechanism of LOX not defined
    • Direct LOX nuclear DNA targets in glioblastoma not mapped
  7. 2015 Medium

    Resolved how LOX-1 ligand binding is structurally constrained and reciprocally coupled to PCSK9, and characterized cholesterol-dependent shedding of soluble LOX-1.

    Evidence Statin docking/MD and dimer-stabilization westerns on the CTLD; reciprocal siRNA and KO mouse studies of LOX-1/PCSK9 with mtROS modulation; MβCD/statin shedding and exosome isolation experiments

    PMID:25950192 PMID:26092101 PMID:26495844

    Open questions at the time
    • Crystallographic confirmation of statin binding absent
    • Identity of the shedding metalloproteinase not defined here
  8. 2016 High

    Established LOX as a disease-causing aortic gene through catalytic-loss mutations and as a nuclear transactivator of SNAI2 driving EMT.

    Evidence Exome sequencing, family segregation, and enzymatic assays of LOX mutants; ChIP and promoter luciferase of LOX on SNAI2 with in vivo thyroid metastasis model

    PMID:26838787 PMID:27029493

    Open questions at the time
    • How nuclear LOX is targeted to specific promoters unknown
    • Relationship between secreted enzymatic LOX and nuclear LOX pool unresolved
  9. 2018 Medium

    Confirmed direct miR-98 targeting of LOX-1 as a brake on foam-cell formation in atherosclerosis.

    Evidence 3'-UTR luciferase reporter, miR-98 mimics/inhibitors in macrophages, agomiR/antagomiR-98 in ApoE-/- mice

    PMID:29549823

    Open questions at the time
    • Single miRNA among broader regulatory network
    • Tissue-specific delivery not addressed
  10. 2019 High

    Defined the proteolytic life cycle of LOX-1 controlling its atherogenic signaling, and placed HIF2A as the specific hypoxic driver of LOX-dependent fibrosis.

    Evidence ADAM10/SPPL2a/b substrate identification, TMD self-association, MAP kinase assays, SPPL2-deficient atherosclerosis mice; HIF2A shRNA/overexpression/inhibitor in orbital fibroblast organoids

    PMID:30388216 PMID:30819724

    Open questions at the time
    • Physiological trigger of ligand-independent NTF signaling in vivo incompletely defined
    • HIF1A-vs-HIF2A selectivity mechanism for LOX not resolved
  11. 2020 High

    Connected LOX-1 turnover to E3 ligase control and tied LOX induction to ECM-driven chemoresistance and immune-cell signaling.

    Evidence HRD1-LOX-1 Co-IP, ubiquitination and KLF2 regulation in endothelium; LOX knockdown across organoids/xenografts/PDX with ITGA5/FN1/FAK-Src epistasis; Th17/Treg co-culture with pathway inhibitors and HF rat model

    PMID:32308114 PMID:32415208 PMID:32649012

    Open questions at the time
    • HRD1 ubiquitination sites on LOX-1 not mapped
    • In vivo durability of LOX-targeted chemosensitization not established
  12. 2024 Medium

    Linked LOX-driven matrix stiffening to mechanotransduction, showing it activates Piezo1 to induce GPX4-dependent ferroptosis in hypoxic-ischemic brain injury.

    Evidence ECM stiffness and LOX activity assays in HIBD models, Piezo1 analysis, pharmacological LOX/Piezo1 inhibition, GPX4 ferroptosis markers, behavioral testing

    PMID:39260063

    Open questions at the time
    • Direct biophysical coupling of LOX cross-links to Piezo1 gating not measured
    • Single-lab pathway requiring orthogonal confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the secreted enzymatic, propeptide tumor-suppressor, and nuclear-transactivator activities of lysyl oxidase are partitioned and coordinated within a single gene product remains unresolved.
  • No structural model linking catalytic, propeptide, and nuclear functions
  • Mechanism of LOX nuclear import and promoter selection unknown
  • Quantitative relationship between extracellular cross-linking and intracellular signaling pools undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 3 GO:0016491 oxidoreductase activity 2 GO:0008289 lipid binding 1 GO:0098772 molecular function regulator activity 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0031012 extracellular matrix 2 GO:0005829 cytosol 1
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
ADAM10FN1HRD1ITGA5PCSK9SNAI2SPPL2A

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 LOX catalytic domain mutations (p.Ser280Arg and p.Ser348Arg) result in significantly lower lysyl oxidase enzymatic activity compared to wild-type protein, and LOX haploinsufficiency predisposes to thoracic aortic aneurysms and dissections, placing LOX as a causal component of aortic structural integrity via its collagen/elastin cross-linking activity. Exome sequencing to identify variants, functional assay of lysyl oxidase enzymatic activity for mutant vs. wild-type protein, segregation analysis in families Circulation research High 26838787
2020 LOX, induced by hypoxia, promotes chemoresistance in triple-negative breast cancer by cross-linking collagen and assembling fibronectin in the ECM; LOX inhibition reduces collagen cross-linking and fibronectin assembly, decreases drug penetration barrier, downregulates ITGA5/FN1 expression, and inhibits FAK/Src signaling, leading to apoptosis and chemosensitization. LOX inhibition/knockdown in 3D cell lines, tumor organoids, xenografts, syngeneic tumors, and PDX models; RNA-sequencing; miR-142-3p re-expression targeting HIF1A/LOX/ITGA5 axis Nature communications High 32415208
2003 LOX (lysyl oxidase) is a copper-dependent amine oxidase that requires a conserved copper binding site, lysyl and tyrosyl residues contributing to quinone cofactor formation, and a cytokine receptor-like domain for function; the N-terminal propeptide domain confers unique regulatory properties distinct from the catalytic C-terminal domain. Structural/domain analysis, comparative expression and sequence analysis across LOX family members including Drosophila orthologs; BMP-1 processing assays Biochimica et biophysica acta Medium 12686136
2019 HIF2A (but not HIF1A) directly induces LOX expression to promote collagen cross-linking and fibrotic ECM deposition in orbital fibroblasts; inhibition of HIF2A or LOX (by shRNA or small molecule antagonists) ameliorated fibrosis in 3D organoids, and constitutively active HIF2A was sufficient to initiate LOX-dependent fibrotic remodeling. shRNA knockdown, small molecule inhibitor experiments, HIF2A overexpression in 3D organoid cultures of human orbital fibroblasts, validated in human TAO tissues Endocrinology High 30388216
2016 LOX transcriptionally activates the SNAI2 promoter (demonstrated by chromatin immunoprecipitation and promoter luciferase assays), and the LOX/SNAI2 axis regulates TIMP4 secretion, thereby mediating epithelial-to-mesenchymal transition and cancer progression. Chromatin immunoprecipitation (ChIP), promoter luciferase assays, siRNA knockdown, in vivo metastatic mouse model of thyroid cancer, protein arrays for MMPs/TIMPs, IHC on patient samples Clinical cancer research High 27029493
2009 A SNP (G473A; Arg158Gln) in the LOX propeptide domain (LOX-PP) profoundly impairs the ability of LOX-PP to inhibit tumor invasion and xenograft tumor formation, identifying the propeptide as the tumor suppressor domain of LOX and demonstrating that the Gln variant cannot oppose LOX enzymatic activity-promoted invasion. Xenograft tumor formation assays, invasion assays comparing Arg158 vs Gln158 LOX-PP variants, comparison of LOX-PP vs. LOX enzymatic effects on invasive phenotype Cancer research High 19654310
2014 LOX promotes RANKL expression in bone marrow stromal cells via production of reactive oxygen species (ROS), which indirectly stimulates osteoclastogenesis; however, LOX cannot substitute for RANKL and does not induce osteoclast differentiation in RANKL-deficient or RANK-deficient cells. In vitro osteoclastogenesis assays with wild-type, RANKL-KO, and RANK-KO cells; LOX injection in RANKL-deficient mice; TRAP staining; resorption pit assays Journal of bone and mineral research High 27606829
2009 LOX gene deficiency in osteoblasts reduces DNA synthesis, impairs mineral nodule formation, and markedly decreases osteoblastic differentiation markers (type I collagen, bone sialoprotein, Runx2/Cbfa1), establishing a role for LOX in osteoblast phenotype beyond extracellular collagen cross-linking. Primary calvarial osteoblasts from Lox(-/-) knockout mice; DNA synthesis assays; annexin-V apoptosis assays; RT-PCR and immunostaining for differentiation markers Calcified tissue international High 19458888
2019 LOX intramembrane proteolysis by SPPL2a/b controls atherogenic LOX-1 (OLR1) signaling: ADAM10 sheds the LOX-1 ectodomain generating N-terminal fragments (NTFs) that self-associate via their transmembrane domains and activate MAP kinases in a ligand-independent manner, upregulating ICAM-1 and CTGF; SPPL2a/b deficiency causes NTF accumulation, enlarging atherosclerotic plaques. Identification of ADAM10 shedding and SPPL2a/b substrates by biochemical assays; MAP kinase activation assays; SPPL2a/b-deficient mouse atherosclerosis models; transmembrane domain self-association experiments The Journal of experimental medicine High 30819724
2006 LOX-1 (OLR1) recognizes phosphatidylserine (PS) in a Ca2+-dependent manner; recombinant glycosylated LOX-1 binds PS but not other phospholipids, and this recognition is maximal with millimolar Ca2+ but not Mg2+; LOX-1-mediated recognition of PS-containing apoptotic bodies is blocked by bivalent-cation chelation or LOX-1-blocking antibodies. In vitro binding assays with recombinant glycosylated LOX-1; cell-based PS recognition assays; Ca2+/Mg2+ substitution; blocking antibodies; PS-containing liposome competition The Biochemical journal High 16146427
2020 HRD1 (E3 ubiquitin ligase) directly interacts with LOX-1 and promotes its ubiquitination and proteasomal degradation; KLF2 transcription factor positively regulates HRD1 expression, and decreased HRD1 leads to LOX-1 accumulation and endothelial apoptosis; LOX-1 deletion attenuated apoptosis caused by HRD1 downregulation. Co-immunoprecipitation (HRD1-LOX-1 interaction), ubiquitination assay, proteasome inhibitor experiments, KLF2 promoter binding assay, HRD1 overexpression/knockdown in endothelial cells, LOX-1 deletion epistasis Cell cycle High 32308114
2015 Statins directly interact with the C-type lectin-like (CTLD) recognition domain of LOX-1, filling the hydrophobic tunnel and stabilizing the LOX-1 dimer assembly; this mechanism underlies statin-mediated inhibition of ox-LDL binding to LOX-1 independent of cholesterol lowering. Cell-based fluorescent ox-LDL displacement binding assay, molecular docking simulations, molecular dynamics simulation, electrophoretic separation and western blot for dimer stabilization Cell cycle Medium 25950192
2003 High glucose induces LOX-1 expression in human aortic endothelial cells at the transcriptional level through increased oxidant stress and activation of NF-κB, PKC, and MAPK signaling; LOX-1 upregulation mediates high glucose-induced monocyte adhesion to endothelium. RT-PCR, protein expression, EMSA (NF-κB binding to LOX-1 promoter), pharmacological inhibitors of NF-κB/PKC/MAPK, anti-LOX-1 antibody blocking monocyte adhesion Diabetes High 12829655
2001 LOX-1 is expressed in human platelets (mRNA and protein) and is stored intracellularly, becoming surface-exposed in an activation-dependent manner; activated platelet LOX-1 mediates ox-LDL binding, and accumulates at thrombus sites in atherosclerotic plaques. RT-PCR, protein detection, flow cytometry on activated vs. resting platelets, anti-LOX-1 antibody blocking of ox-LDL binding, immunohistochemistry of atherosclerotic plaque Biochemical and biophysical research communications Medium 11263985
2011 microRNA let-7g negatively regulates LOX-1 expression via a binding site in the 3'-UTR of LOX-1 mRNA; ox-LDL reduces let-7g expression through a Ca2+-activated PKC pathway; OCT-1 represses let-7g promoter activity; let-7g overexpression inhibits ox-LDL-induced LOX-1/OCT-1 expression and cell proliferation and migration. 3'-UTR luciferase reporter assay confirming let-7g binding site, promoter assay for OCT-1 binding to let-7g promoter, chromatin immunoprecipitation (ChIP), transfection of let-7g mimics/inhibitors, Ca2+/PKC inhibitor studies Journal of cell science High 22135361
2014 LOX-1 activation in macrophages drives ROS generation, mitochondrial DNA damage, and autophagy, which together activate the NLRP3 inflammasome; LOX-1 inhibition (antibody or siRNA) suppresses ROS, autophagy, mtDNA damage, and NLRP3 activation; DNase II knockdown inhibits autophagy and NLRP3 inflammasome downstream of damaged mtDNA. LOX-1 siRNA/antibody inhibition in THP-1 macrophages and primary macrophages, ROS inhibitors, autophagy inducer/inhibitor, DNase II knockdown, NLRP3 inflammasome activation assays Cardiovascular research High 24776598
2015 LOX (lysyl oxidase) and PCSK9 positively regulate each other's expression in vascular cells; siRNA knockdown of PCSK9 reduces LOX-1 expression and function; LOX-1 knockdown reduces PCSK9 expression; LOX-1 KO mice express less PCSK9 and PCSK9-KO mice express less LOX-1; mitochondrial ROS initiates this mutual regulation, acting upstream of both. siRNA transfection (PCSK9 and LOX-1 knockdown), recombinant hPCSK9 treatment, LOX-1 cDNA overexpression, LOX-1 and PCSK9 KO mouse studies, mtROS induction/inhibition Cardiovascular research High 26092101
2001 Statins (simvastatin, atorvastatin) reduce ox-LDL-induced LOX-1 upregulation and simultaneously prevent LOX-1-mediated suppression of eNOS expression; LOX-1 activation by ox-LDL also activates MAP kinase, and statin attenuation of MAP kinase provides a mechanism for eNOS restoration. Human coronary artery endothelial cells treated with ox-LDL ± statins; LOX-1 and eNOS expression by western blot; MAP kinase activation assay Biochemical and biophysical research communications Medium 11735125
2000 TGF-β1 differentially regulates scavenger receptors in human macrophages: it decreases CD36 and SR-A expression while upregulating LOX-1 mRNA, thereby altering the balance of modified LDL uptake and foam cell formation. RT-PCR and flow cytometry in THP-1 cells and primary human monocytes treated with TGF-β1; measurements of scavenger receptor expression and total ox-LDL uptake American journal of physiology. Heart and circulatory physiology Medium 10749696
2014 LOX inhibition (by BAPN) in glioblastoma cell lines reduces migration, invasion, and soft agar colony formation; LOX protein localizes to cytoplasm and nucleus, with nuclear localization being lower in IDH1-mutant glioblastoma. siRNA knockdown and BAPN pharmacological inhibition of LOX in U87MG and A172 glioblastoma cell lines; migration, invasion, and colony formation assays; immunohistochemistry for subcellular localization PloS one Medium 25790191
2014 miR30a directly targets and represses LOX expression (identified as a direct target via miRNA target prediction validated experimentally); LOX inhibition decreases cellular invasion, migration, EMT marker levels, and metastatic capacity in thyroid cancer models in vitro and in vivo. miR30a mimic/inhibitor transfections, LOX expression analysis, in vitro invasion/migration assays, in vivo metastasis model; LOX identified as direct miR30a target Cancer research Medium 25488748
2020 Th17 cells promote LOX expression via the IL-17/ERK1/2-AP-1 signaling pathway, while Tregs inhibit LOX expression via the IL-10/JAK1-STAT3 pathway; LOX upregulation mediates increased collagen cross-linking and myocardial fibrosis in cardiac fibroblasts. Co-culture of cardiac fibroblasts with polarized Th17/Treg cells; BAPN LOX inhibitor; signaling pathway inhibitors; adoptive transfer in HF rat model; LOX expression and collagen deposition measurements Acta physiologica Medium 32649012
2024 LOX-mediated ECM cross-linking increases tissue stiffness, which activates mechanosensitive Piezo1 channels in neurons; Piezo1 activation induces ferroptosis in a GPX4-dependent manner in hypoxic-ischemic brain damage; pharmacological LOX inhibition with traumatic acid (identified as a novel LOX inhibitor) reduces neuronal ferroptosis and improves neurological outcomes. LOX activity measurement in HIBD models in vivo and in vitro, ECM stiffness assays, Piezo1 expression/activation analysis, LOX/Piezo1 pharmacological inhibition, LOX inhibitor (traumatic acid) enzymatic activity assay, ferroptosis markers (GPX4), behavioral testing Redox biology Medium 39260063
2003 LOX-1 pathway activation in cardiomyocytes following ischemia-reperfusion (but not ischemia alone) contributes to myocardial infarction; anti-LOX-1 monoclonal antibody treatment reduced myocardial infarction size by ~50% in a rat coronary artery ligation/reperfusion model. Rat ischemia-reperfusion model; immunohistochemistry for LOX-1 induction in cardiomyocytes; anti-LOX-1 monoclonal antibody treatment; infarct size quantification Biochemical and biophysical research communications Medium 12507499
2018 miR-98 directly targets LOX-1 (confirmed by luciferase reporter assay on LOX-1 3'-UTR); miR-98 enhancement decreases LOX-1 expression and inhibits foam cell formation and lipid accumulation in macrophages; antagomiR-98 increases LOX-1 and promotes foam cell formation in ApoE-/- mice. Luciferase reporter assay confirming direct miR-98 targeting of LOX-1 3'-UTR; miR-98 mimics/inhibitors in mouse peritoneal macrophages; agomiR/antagomiR-98 in ApoE-/- mice on high-fat diet; LOX-1 expression and foam cell/lipid accumulation quantification Redox biology Medium 29549823
2015 Membrane cholesterol depletion by MβCD or statins triggers LOX-1 shedding: cholesterol depletion promotes release of LOX-1 in exosomes as full-length transmembrane isoform and as a truncated soluble ectodomain fragment (sLOX-1) generated by a secreted metalloproteinase; long-term statin treatment enhances sLOX-1 proteolytic shedding. Cholesterol modulation with MβCD and statins in LOX-1-expressing cells and EA.hy926 endothelial cells; exosome isolation; western blot for full-length and truncated sLOX-1 forms; metalloproteinase activity experiments PloS one Medium 26495844

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 LOX-1, OxLDL, and atherosclerosis. Mediators of inflammation 603 23935243
1998 Inducible gene targeting in mice using the Cre/lox system. Methods (San Diego, Calif.) 549 9608509
2004 Cre-lox-regulated conditional RNA interference from transgenes. Proceedings of the National Academy of Sciences of the United States of America 518 15240889
2020 Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Nature communications 294 32415208
2019 Role of Ox-LDL and LOX-1 in Atherogenesis. Current medicinal chemistry 252 29737246
2011 Oxidized LDL, LOX-1 and atherosclerosis. Cardiovascular drugs and therapy 243 21947818
2012 LOX-1 in atherosclerosis: biological functions and pharmacological modifiers. Cellular and molecular life sciences : CMLS 242 23124189
2020 Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis. Hepatology (Baltimore, Md.) 226 32176358
2003 Structural and functional diversity of lysyl oxidase and the LOX-like proteins. Biochimica et biophysica acta 208 12686136
2019 LOX-1: Regulation, Signaling and Its Role in Atherosclerosis. Antioxidants (Basel, Switzerland) 205 31336709
2015 Cross-talk between LOX-1 and PCSK9 in vascular tissues. Cardiovascular research 205 26092101
2018 Detecting and Avoiding Problems When Using the Cre-lox System. Trends in genetics : TIG 199 29336844
2006 Cre-lox-based system for multiple gene deletions and selectable-marker removal in Lactobacillus plantarum. Applied and environmental microbiology 188 17142375
2020 PCSK9 and inflammation: role of shear stress, pro-inflammatory cytokines, and LOX-1. Cardiovascular research 184 31746997
2016 LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections. Circulation research 176 26838787
2017 LOX-1 in Atherosclerosis and Myocardial Ischemia: Biology, Genetics, and Modulation. Journal of the American College of Cardiology 143 28571642
2001 Activation-dependent surface expression of LOX-1 in human platelets. Biochemical and biophysical research communications 132 11263985
2011 The discovery of LOX-1, its ligands and clinical significance. Cardiovascular drugs and therapy 130 21805404
2007 Regulation of COX and LOX by curcumin. Advances in experimental medicine and biology 130 17569213
2014 LOX-1, mtDNA damage, and NLRP3 inflammasome activation in macrophages: implications in atherogenesis. Cardiovascular research 117 24776598
2018 LOX-1 receptor: A potential link in atherosclerosis and cancer. Life sciences 112 29462603
2020 Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways. Biomolecules 107 32708046
2012 Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. Investigative ophthalmology & visual science 105 22661479
2009 Lox-1: the multifunctional receptor underlying cardiovascular dysfunction. Circulation journal : official journal of the Japanese Circulation Society 101 19801851
2001 Inhibition of LOX-1 by statins may relate to upregulation of eNOS. Biochemical and biophysical research communications 95 11735125
2011 Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1. Journal of cell science 92 22135361
2003 Glucose enhances endothelial LOX-1 expression: role for LOX-1 in glucose-induced human monocyte adhesion to endothelium. Diabetes 91 12829655
2021 LOX-1 and cancer: an indissoluble liaison. Cancer gene therapy 89 33402733
2021 Cas12a-assisted precise targeted cloning using in vivo Cre-lox recombination. Nature communications 89 33608525
2006 Differential expression within the LOX gene family in ripening kiwifruit. Journal of experimental botany 87 17032731
2014 LOX-1 and ROS, inseparable factors in the process of endothelial damage. Free radical research 82 24886290
2019 HIF2A-LOX Pathway Promotes Fibrotic Tissue Remodeling in Thyroid-Associated Orbitopathy. Endocrinology 81 30388216
2014 Platelet 12-LOX is essential for FcγRIIa-mediated platelet activation. Blood 81 25100742
2000 TGF-beta1 downregulates CD36 and scavenger receptor A but upregulates LOX-1 in human macrophages. American journal of physiology. Heart and circulatory physiology 80 10749696
2006 LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells. The Biochemical journal 79 16146427
2018 Targeting LOX-1 in atherosclerosis and vasculopathy: current knowledge and future perspectives. Annals of the New York Academy of Sciences 77 30381837
2017 Human colorectal cancer progression correlates with LOX-induced ECM stiffening. International journal of biological sciences 73 29209148
2014 miR30a inhibits LOX expression and anaplastic thyroid cancer progression. Cancer research 71 25488748
2019 Interplay Between LOX Enzymes and Integrins in the Tumor Microenvironment. Cancers 62 31130685
2016 LOX-1-Mediated Effects on Vascular Cells in Atherosclerosis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 59 27160316
2016 Lysyl Oxidase (LOX) Transcriptionally Regulates SNAI2 Expression and TIMP4 Secretion in Human Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 58 27029493
2009 A loss-of-function polymorphism in the propeptide domain of the LOX gene and breast cancer. Cancer research 57 19654310
2010 Good planning and serendipity: exploiting the Cre/Lox system in the testis. Reproduction (Cambridge, England) 53 21084571
2009 Lysyl oxidase (lox) gene deficiency affects osteoblastic phenotype. Calcified tissue international 53 19458888
2019 Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships. Journal of medicinal chemistry 52 31070916
2003 Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas. Anticancer research 50 12820424
2016 Roles of LOX-1 in microvascular dysfunction. Microvascular research 47 26907636
2012 LOX-1: a multiligand receptor at the crossroads of response to danger signals. Current opinion in lipidology 47 22777292
2000 Oxidized-LDL and atherosclerosis. Role of LOX-1. Annals of the New York Academy of Sciences 47 10865829
2000 Inflammatory 5-LOX mRNA and protein are increased in brain of aging rats. Neurobiology of aging 47 11016533
2022 Dysregulation of interaction between LOXhigh fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection. Theranostics 46 34976220
2020 Th17/Treg imbalance modulates rat myocardial fibrosis and heart failure by regulating LOX expression. Acta physiologica (Oxford, England) 46 32649012
2019 LOX-1 and atherosclerotic-related diseases. Clinica chimica acta; international journal of clinical chemistry 46 30639239
2014 FLP/FRT and Cre/lox recombination technology in C. elegans. Methods (San Diego, Calif.) 46 24874786
2014 LOX-1, oxidant stress, mtDNA damage, autophagy, and immune response in atherosclerosis. Canadian journal of physiology and pharmacology 46 24959993
2015 LOX expression and functional analysis in astrocytomas and impact of IDH1 mutation. PloS one 45 25790191
2001 Identification of peptides that target the endothelial cell-specific LOX-1 receptor. Hypertension (Dallas, Tex. : 1979) 45 11230317
2016 LOX Fails to Substitute for RANKL in Osteoclastogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 44 27606829
2016 LOX-1 and TLR4 affect each other and regulate the generation of ROS in A. fumigatus keratitis. International immunopharmacology 43 27694040
2015 Molecular mechanism of statin-mediated LOX-1 inhibition. Cell cycle (Georgetown, Tex.) 43 25950192
2023 Single-cell analysis reveals lysyl oxidase (Lox)+ fibroblast subset involved in cardiac fibrosis of diabetic mice. Journal of advanced research 42 36706988
2018 Inhibition of the LOX enzyme family members with old and new ligands. Selectivity analysis revisited. Bioorganic & medicinal chemistry letters 42 30098867
2011 LOX-1 and angiotensin receptors, and their interplay. Cardiovascular drugs and therapy 41 21861069
2003 LOX-1 pathway affects the extent of myocardial ischemia-reperfusion injury. Biochemical and biophysical research communications 41 12507499
2018 MicroRNA-98 regulates foam cell formation and lipid accumulation through repression of LOX-1. Redox biology 40 29549823
2017 Xanthine Oxidase Induces Foam Cell Formation through LOX-1 and NLRP3 Activation. Cardiovascular drugs and therapy 40 28084571
2014 LOX-1 in atherosclerotic disease. Clinica chimica acta; international journal of clinical chemistry 40 25463747
2019 LOX and ACSL5 as potential relapse markers for pancreatic cancer patients. Cancer biology & therapy 36 30712446
2021 Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer. Current pharmaceutical design 35 33388012
2017 LOX-1 and Its Splice Variants: A New Challenge for Atherosclerosis and Cancer-Targeted Therapies. International journal of molecular sciences 35 28146073
2019 Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis. The Journal of experimental medicine 34 30819724
2019 Upregulated LOX-1 Receptor: Key Player of the Pathogenesis of Atherosclerosis. Current atherosclerosis reports 34 31350594
2013 Oxidized LDL and LOX-1 in experimental sepsis. Mediators of inflammation 32 24000272
2011 LOX-1 transcription. Cardiovascular drugs and therapy 31 21796333
2012 The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease. Cardiology research and practice 30 22454776
2011 LOX-1 and obesity. Cardiovascular drugs and therapy 30 21881850
2007 Expression of 5-lipoxygenase (5-LOX) in T lymphocytes. Immunology 28 17484769
2020 LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma. Biomarker research 27 31921422
2020 HRD1 prevents atherosclerosis-mediated endothelial cell apoptosis by promoting LOX-1 degradation. Cell cycle (Georgetown, Tex.) 27 32308114
2019 Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes. Cell death & disease 27 30718451
2014 Berberine combined with atorvastatin downregulates LOX‑1 expression through the ET‑1 receptor in monocyte/macrophages. International journal of molecular medicine 27 24756769
2011 Novel concepts in the genesis of hypertension: role of LOX-1. Cardiovascular drugs and therapy 26 21912849
2018 Toll-like receptor 2 activation primes and upregulates osteoclastogenesis via lox-1. Lipids in health and disease 24 29859535
2015 Membrane Cholesterol Modulates LOX-1 Shedding in Endothelial Cells. PloS one 24 26495844
2011 Angiogenesis is a link between atherosclerosis and tumorigenesis: role of LOX-1. Cardiovascular drugs and therapy 24 21968594
2022 Cre/lox regulated conditional rescue and inactivation with zebrafish UFlip alleles generated by CRISPR-Cas9 targeted integration. eLife 23 35713402
2012 Plant 9-lox oxylipin metabolism in response to arbuscular mycorrhiza. Plant signaling & behavior 23 23073021
2021 Effects of Apigenin on the Expression of LOX-1, Bcl-2, and Bax in Hyperlipidemia Rats. Chemistry & biodiversity 22 34118114
2020 LOX-1: A potential driver of cardiovascular risk in SLE patients. PloS one 22 32182251
1994 TKO'ed: lox, stock and barrel. BioEssays : news and reviews in molecular, cellular and developmental biology 22 7840765
2022 Identification of the LOX Gene Family in Peanut and Functional Characterization of AhLOX29 in Drought Tolerance. Frontiers in plant science 21 35356112
2021 Urine LOX-1 and Volatilome as Promising Tools towards the Early Detection of Renal Cancer. Cancers 21 34439368
2013 TAILOR: transgene activation and inactivation using lox and rox in zebrafish. PloS one 21 24391998
2008 5-LOX, 12-LOX and 15-LOX in immature forms of human leukemic blasts. Leukemia research 21 18561999
2024 LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review. International journal of molecular sciences 20 38791315
2022 Cre/lox-Mediated Chromosomal Integration of Biosynthetic Gene Clusters for Heterologous Expression in Aspergillus nidulans. ACS synthetic biology 20 35168324
2018 Overexpression of Lox in triple-negative breast cancer. Annals of diagnostic pathology 20 29661738
2011 LOX-1/LOXIN: the yin/yang of atheroscleorosis. Cardiovascular drugs and therapy 20 21904818
2024 LOX-mediated ECM mechanical stress induces Piezo1 activation in hypoxic-ischemic brain damage and identification of novel inhibitor of LOX. Redox biology 19 39260063
2006 Lysyl oxidase (LOX) and hypoxia-induced metastases. Cancer biology & therapy 19 16969095

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