Affinage

ANGPTL2

Angiopoietin-related protein 2 · UniProt Q9UKU9

Length
493 aa
Mass
57.1 kDa
Annotated
2026-06-09
72 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANGPTL2 is a secreted glycoprotein that functions as a multireceptor ligand coupling tissue stress and inflammation to cellular activation, vascular remodeling, tumor progression, and tissue regeneration (PMID:24526691, PMID:22345152, PMID:31581797). It engages at least four distinct receptors with context-specific outputs: it binds LILRB2 through its C-terminal fibronectin domain, an interaction requiring ligand multimerization and the first and fourth Ig domains of the receptor, to drive proliferative and inflammatory signaling, while membrane-anchored N-terminal ANGPTL2 activates LILRB2 more potently than the soluble form (PMID:24899623, PMID:35675737); it signals through integrin α5β1 to activate ERK, JNK, p38, AKT, and NF-κB in chondrocytes, macrophages, and tumor cells (PMID:31581797, PMID:27402837); it acts as a CD146 ligand on adipocytes to activate CREB during adipogenesis and adipose inflammation (PMID:33747748); and it binds the myelin-associated glycoprotein MAG to recruit Fyn kinase and transactivate MYRF, promoting oligodendrocyte differentiation and remyelination (PMID:36855057). Through NF-κB activation in endothelial cells, macrophages, and fibroblasts, ANGPTL2 promotes chronic inflammation, monocyte chemotaxis, endothelial dysfunction, and accelerated atherosclerosis (PMID:24526691, PMID:37736764, PMID:33051596). In cancer it acts in an autocrine/paracrine manner to enhance tumor cell motility, invasion, and metastasis via integrin α5β1/p38/MMP signaling, and promotes immune evasion by accelerating PRC2-mediated repression of MHC-I and by generating myeloid-derived suppressor cells (PMID:22345152, PMID:24448647, PMID:37452654, PMID:39321028). Its activity is tuned at multiple levels: HIF1A transcriptionally activates ANGPTL2 in a positive feedback loop (PMID:34974813), promoter CpG methylation represses its expression (PMID:27101308), CSN5 binding stabilizes the protein by reducing its ubiquitination (PMID:33508120), and TLL1 protease cleaves ANGPTL2 into inactive fragments (PMID:24448647). In the heart, ANGPTL2 has both injurious roles—inactivating AKT-SERCA2a signaling and activating the NLRP3 inflammasome via DUSP1 suppression—and protective roles, interacting with and repressing NOX4 to limit oxidative left ventricular dysfunction (PMID:27677409, PMID:37531825, PMID:38426206).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2012 High

    Established that tumor-cell ANGPTL2 is functionally pro-metastatic and identified its transcriptional upstream regulators, framing it as an autocrine/paracrine driver of cancer aggressiveness.

    Evidence In vitro motility/invasion assays with knockdown/overexpression and xenograft models; NFATc/ATF2/c-Jun overexpression

    PMID:22345152

    Open questions at the time
    • Receptor mediating these tumor cell effects not defined in this study
    • No structural basis for autocrine signaling
  2. 2014 High

    Identified LILRB2 as a direct ANGPTL2 receptor and mapped the binding determinants, defining the first molecular receptor interaction and the requirement for ligand multimerization.

    Evidence Co-IP, LILRB2 reporter activation assays, domain mutagenesis, ex vivo HSC expansion

    PMID:24899623 PMID:35675737

    Open questions at the time
    • Downstream signaling cascade from LILRB2 not fully resolved here
    • In vivo relevance of HSC expansion to disease not addressed
  3. 2014 High

    Demonstrated that ANGPTL2 promotes metastasis through integrin α5β1/p38/MMP signaling and that TLL1 proteolytic cleavage inactivates it, revealing both a receptor pathway and a regulatory cleavage mechanism.

    Evidence Xenograft models, integrin blocking, in vitro TLL1 cleavage assays, overexpression/knockdown

    PMID:24448647

    Open questions at the time
    • In vivo significance of TLL1 cleavage not established
    • Relationship between integrin and LILRB2 signaling unresolved
  4. 2014 High

    Showed that endothelial ANGPTL2 drives proinflammatory NF-κB signaling and atherosclerosis, linking the ligand to chronic vascular inflammation in vivo.

    Evidence Angptl2 KO in ApoE-null mice, Tie2-driven transgenics, bone marrow transplantation, in vitro NF-κB and chemotaxis assays

    PMID:24526691

    Open questions at the time
    • Endothelial receptor mediating NF-κB activation not identified
    • Whether circulating vs. local ANGPTL2 drives the effect unclear
  5. 2016 High

    Distinguished integrin α5β1 (not PirB/LILRB) as the macrophage receptor for ANGPTL2 inflammatory signaling and tied it to antibacterial innate immunity, establishing cell-type-specific receptor usage.

    Evidence Angptl2-deficient BMDMs, integrin pathway analysis, Salmonella infection model, NO measurement

    PMID:27402837

    Open questions at the time
    • Molecular events downstream of integrin in macrophages not fully mapped
    • Reconciliation with LILRB2-dependent contexts not addressed
  6. 2016 High

    Defined cardiac ANGPTL2 as a suppressor of AKT-SERCA2a signaling and myocardial energetics, providing a mechanism for stress-induced cardiac dysfunction.

    Evidence Cardiac-specific transgenic and KO mice, pressure overload, siRNA knockdown, echocardiography

    PMID:27677409

    Open questions at the time
    • Cardiac receptor mediating AKT-SERCA2a inactivation unidentified
    • Direct vs. indirect effect on SERCA2a unresolved
  7. 2016 Medium

    Revealed tissue-protective roles for ANGPTL2, with epithelial/alveolar macrophage-derived ANGPTL2 limiting lung fibrosis, and promoter DNA methylation controlling its expression, broadening the model beyond purely pathogenic signaling.

    Evidence Angptl2 KO mice with bleomycin and bone marrow transplant; luciferase assays with methylated promoter and bisulfite pyrosequencing

    PMID:27101308 PMID:27542805

    Open questions at the time
    • Mechanism by which ANGPTL2 protects against fibrosis not defined
    • Single-lab findings for both protection and methylation
  8. 2017 High

    Showed ANGPTL2 from intestinal stromal cells maintains the stem cell niche via BMP/β-catenin balance, establishing a homeostatic developmental role in epithelial regeneration.

    Evidence Angptl2-deficient mice, intestinal injury model, Lgr5 and β-catenin activity assays

    PMID:28043948

    Open questions at the time
    • Receptor transducing the niche signal not identified
    • Direct vs. indirect regulation of β-catenin unclear
  9. 2021 High

    Identified CD146 as a third ANGPTL2 receptor on adipocytes acting through CREB, and showed a VPS33B-controlled extracellular vesicle route delivering ANGPTL2 to LILRB2 in leukemia, diversifying both receptor repertoire and delivery mode.

    Evidence Co-IP, CD146 KO in adipocytes, anti-CD146 antibody obesity model; Vps33b conditional KO lines and MLL-AF9 AML model with SEV cargo analysis

    PMID:33108353 PMID:33747748

    Open questions at the time
    • Structural basis of CD146 binding not defined
    • Whether SEV delivery operates in non-leukemic contexts unknown
  10. 2021 Medium

    Defined post-translational stabilization of ANGPTL2 by CSN5-mediated deubiquitination, adding protein-level control to its regulation.

    Evidence Co-IP and ubiquitination assays with CSN5 gain/loss in thyroid carcinoma cells

    PMID:33508120

    Open questions at the time
    • E3 ligase opposing CSN5 not identified
    • Single-lab, single-tumor-type finding
  11. 2022 Medium

    Established a HIF1A-ANGPTL2 positive feedback loop, linking hypoxic stress responses to ANGPTL2 expression in cardiomyocytes.

    Evidence Luciferase reporter and ChIP assays, ANGPTL2 and HIF1A knockdown in H9c2 cells, Nrf2/HO-1 analysis

    PMID:34974813

    Open questions at the time
    • In vivo confirmation lacking
    • Single-lab, in vitro only
  12. 2023 High

    Identified MAG as a novel ANGPTL2 receptor coupling to Fyn kinase and MYRF transactivation, revealing a regenerative role in oligodendrocyte differentiation and remyelination.

    Evidence Receptor binding assays, Angptl2-null/Mag-null single and double KO mice, cuprizone demyelination model, phosphorylation and differentiation assays

    PMID:36855057

    Open questions at the time
    • How MAG binding relates to other ANGPTL2 receptors unknown
    • Direct vs. co-receptor role of MAG not resolved
  13. 2023 Medium

    Connected ANGPTL2-integrin α5β1 signaling to tumor immune evasion through PRC2-mediated MHC-I repression, extending its cancer role to adaptive immunity.

    Evidence ANGPTL2-deficient tubular cells in tRCC model, IFN-γ-induced MHC-I assays, integrin blocking, CD8+ T-cell cytotoxicity

    PMID:37452654

    Open questions at the time
    • Link between integrin signaling and PRC2 recruitment not mechanistically defined
    • Single-lab finding
  14. 2023 Medium

    Defined context-dependent immune and cardiac mechanisms, including DUSP1-suppression-driven NLRP3 inflammasome activation and NF-κB-driven chemoattractant production, sharpening ANGPTL2's role in inflammatory disease.

    Evidence Cardiac AAV overexpression/knockdown with DUSP1 and NLRP3 manipulation in septic cardiomyopathy; ANGPTL2-deficient mice in ICI myocarditis with NF-κB analysis

    PMID:37531825 PMID:37736764

    Open questions at the time
    • Receptors upstream of DUSP1 suppression not identified
    • Single-lab findings
  15. 2024 Medium

    Revealed an ANGPTL2-NOX4 physical interaction that restrains cardiac oxidative stress, identifying a protective, redox-regulatory function distinct from its inflammatory roles.

    Evidence Co-IP in HEK293, ANGPTL2 knockdown mice with AAV9-shRNA NOX4 rescue, echocardiography, H2O2 measurement

    PMID:38426206

    Open questions at the time
    • Whether intracellular vs. secreted ANGPTL2 binds NOX4 unclear
    • Single-lab finding
  16. 2025 Medium

    Extended ANGPTL2 signaling to metabolic disease, showing adipocyte-secreted ANGPTL2 inhibits renal AKT/ABCG2 signaling to promote hyperuricemia.

    Evidence Angptl2 KO and adipocyte-specific overexpression mice, recombinant ANGPTL2 in HK-2/RTEC cells, AKT/ABCG2 analysis, adipose proteomics

    PMID:40180020

    Open questions at the time
    • Renal receptor for ANGPTL2 not identified
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single secreted ligand selects among integrin α5β1, LILRB2, CD146, and MAG to produce opposing pro-inflammatory, pro-tumor, protective, and regenerative outcomes in different tissues remains unresolved.
  • No unifying structural model of receptor selection
  • Roles of multimerization, membrane anchoring, and proteolytic cleavage in directing receptor choice not integrated
  • Conditions favoring protective vs. pathogenic signaling not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 4
Localization
GO:0005576 extracellular region 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4
Partners
CD146CSN5ITGA5ITGB1LILRB2MAGNOX4TLL1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 ANGPTL2 binds to LILRB2 (leukocyte immunoglobulin-like receptor B2) to activate downstream signaling; ligand multimerization is required for LILRB2 activation; the first and fourth Ig domains of LILRB2 contain a motif necessary for ANGPTL2 binding and activation; the fibronectin (FBN) domain at the C-terminus of ANGPTL2 is essential for LILRB2 stimulation. Co-immunoprecipitation, LILRB2 reporter activation assays, domain mutagenesis, ex vivo HSC expansion assays Blood High 24899623 35675737
2014 Endothelial cell-derived ANGPTL2 activates proinflammatory NF-κB signaling in endothelial cells and increases monocyte/macrophage chemotaxis, leading to endothelial dysfunction and accelerated atherosclerosis progression. Angptl2 knockout in ApoE-deficient mice, Tie2-promoter-driven Angptl2 transgenic mice, bone marrow transplantation experiments, in vitro NF-κB signaling assays, monocyte chemotaxis assay Arteriosclerosis, thrombosis, and vascular biology High 24526691
2012 Tumor cell-derived ANGPTL2 promotes tumor cell motility and invasion in an autocrine/paracrine manner, and accelerates metastasis in xenograft mouse models; transcription factors NFATc, ATF2, and c-Jun upregulate ANGPTL2 expression in aggressive tumor cells. In vitro motility and invasion assays, ANGPTL2 knockdown/overexpression, xenograft mouse models, transcription factor overexpression Cancer research High 22345152
2014 ANGPTL2 promotes osteosarcoma metastasis via integrin α5β1, p38 MAPK, and matrix metalloproteinases by promoting tumor cell intravasation; TLL1 (tolloid-like 1) protease cleaves ANGPTL2 into fragments in vitro that do not enhance tumor progression. Xenograft mouse models, integrin blocking, in vitro cleavage assays with TLL1 protease, ANGPTL2 overexpression and knockdown Science signaling High 24448647
2016 ANGPTL2 in the pathologically stressed heart inactivates AKT and SERCA2a signaling and decreases myocardial energy metabolism, causing cardiac dysfunction; Angptl2 knockout mice show increased left ventricular contractility and upregulated AKT-SERCA2a signaling. Cardiac-specific ANGPTL2 transgenic mice, Angptl2 knockout mice, pressure overload model, ANGPTL2 knockdown via siRNA, echocardiography, AKT/SERCA2a pathway analysis Nature communications High 27677409
2017 ANGPTL2-mediated intestinal stromal cell (ISEMF) signaling maintains the intestinal stem cell niche by modulating competing BMP and β-catenin signaling; ANGPTL2 deficiency decreases Lgr5 expression and β-catenin transcriptional activity, and impairs epithelial regeneration after injury. Angptl2-deficient mice, intestinal injury model, Lgr5 expression analysis, β-catenin activity assay, cell-type-specific expression analysis The EMBO journal High 28043948
2015 ANGPTL2 binds LILRB2 to support the growth of lung cancer cells; the SHP2/CaMK1/CREB axis controls proliferation of lung cancer cell lines downstream of ANGPTL2-LILRB2 signaling. LILRB2 knockdown in NSCLC cell lines, proliferation and colony formation assays, migration assay, mechanistic pathway analysis Oncotarget Medium 26056041
2015 Tumor cell-derived ANGPTL2 increases CXCR4 expression in breast cancer cells, enhancing their responsiveness to CXCL12 and promoting bone metastasis; ANGPTL2 knockdown attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression. ANGPTL2 knockdown in breast cancer cells, intracardiac injection xenograft model, CXCR4 expression analysis, CXCL12 migration assays Scientific reports Medium 25773070
2019 ANGPTL2 signals through integrin α5β1 in chondrocytes to activate phosphorylation of ERK, JNK, p38, Akt, and NF-κB, inducing expression of inflammatory factors; inhibiting integrin α5β1 suppresses these inflammatory reactions. ANGPTL2 treatment of ATDC5 cells, anti-integrin α5β1 antibody blocking, western blotting for MAPK/Akt/NF-κB phosphorylation, RT-PCR for inflammatory markers Cartilage Medium 31581797
2016 ANGPTL2 inflammatory signaling in macrophages is transduced through integrin α5β1 (not through paired immunoglobulin-like receptor B); ANGPTL2 promotes proinflammatory macrophage activity and nitric oxide production required for innate immune responses against bacterial infection. Angptl2-deficient mouse bone marrow-derived macrophages, integrin α5β1 pathway analysis, Salmonella infection model, NO production measurement, proinflammatory marker expression The Journal of biological chemistry High 27402837
2021 ANGPTL2 acts as a CD146 ligand on adipocytes; ANGPTL2 binds CD146 to activate CREB, which upregulates CD146 expression during adipogenesis and adipose inflammation; CD146 ablation suppresses adipogenesis and lipid accumulation; anti-CD146 antibodies inhibit obesity by disrupting CD146-ANGPTL2 interactions. Co-immunoprecipitation, CD146 knockout in preadipocytes and adipocytes, CREB signaling analysis, anti-CD146 antibody treatment, in vivo obesity model Advanced science High 33747748
2021 Endothelial cell-derived small extracellular vesicles (SEVs) contain ANGPTL2, which accelerates AML leukemia progression via binding to the LILRB2 receptor; VPS33B governs the release of ANGPTL2-containing SEVs from endothelial cells. Cell-type-specific Vps33b conditional knockout (7 Cre lines), MLL-AF9 AML mouse model, protein analysis of SEV cargo, LILRB2 receptor binding assay, primary human AML cell maintenance assay The Journal of clinical investigation High 33108353
2021 ANGPTL2 induces inflammatory factor expression via LILRB2 in human fibroblast-like synoviocytes, activating ERK, p38, JNK, NF-κB, and Akt phosphorylation; anti-LILRB2 antibody pretreatment inhibits these effects. Recombinant ANGPTL2 treatment of HFLS cells, anti-LILRB2 antibody blocking, RT-PCR, western blotting for MAPK/NF-κB/Akt phosphorylation Inflammation Medium 33538932
2022 Tumor cell-derived ANGPTL2 upregulates OB-cadherin expression, which interacts with β-catenin and blocks destruction complex-independent proteasomal degradation of β-catenin, thereby augmenting β-catenin pathway signaling and promoting colorectal cancer cell proliferation; increased ANGPTL2 in CRC cells is accompanied by decreased surface integrin α5β1 expression. ANGPTL2 deficiency in mouse intestinal tumor model, CRC cell overexpression/knockdown, OB-cadherin expression analysis, β-catenin interaction and degradation assays, integrin α5β1 surface expression analysis Oncogene Medium 35831580
2023 ANGPTL2 binds MAG (myelin-associated glycoprotein) as a novel receptor, enhances MAG phosphorylation, recruits Fyn kinase, increases Fyn phosphorylation, and transactivates MYRF to promote oligodendrocyte differentiation and myelination; ANGPTL2-mediated remyelination depends on MAG receptor. Receptor identification and binding assay, Angptl2-null and Mag-null mice, cuprizone demyelination model, Angptl2-null/Mag-null double knockout, phosphorylation assays, HCN cell differentiation in vitro Cell & bioscience High 36855057
2023 The ANGPTL2-α5β1 integrin pathway accelerates polycomb repressive complex 2 (PRC2)-mediated epigenetic repression of MHC-I expression in tumor cells, reducing susceptibility to CD8+ T-cell-mediated anti-tumor immune responses. ANGPTL2-deficient renal tubular epithelial cells in tRCC mouse model, IFN-γ-induced MHC-I expression assays, integrin α5β1 pathway blocking, PRC2 complex involvement analysis, CD8+ T-cell cytotoxicity assays Molecular oncology Medium 37452654
2023 Cardiac myofibroblast-derived ANGPTL2 enhances expression of chemoattractants via the NF-κB pathway, accelerating T cell recruitment into heart tissues during ICI-related autoimmune myocarditis. ANGPTL2-deficient mice in ICI-related autoimmune myocarditis model, cardiac fibroblast ANGPTL2 expression analysis, NF-κB pathway analysis, immune cell infiltration quantification Communications biology Medium 37736764
2023 ANGPTL2 promotes VEGF-A synthesis in lung cancer cells; integrin α5β1, p38, and NF-κB signaling mediate ANGPTL2-regulated lymphangiogenesis. ANGPTL2 overexpression in lung cancer cells, VEGF-A measurement, pathway inhibition (integrin α5β1, p38, NF-κB), LEC tube formation and migration assays, in vivo tumor growth and lymphangiogenesis model Aging Medium 36917086
2023 ANGPTL2 activates NLRP3 inflammasome via suppressing DUSP1 signaling in cardiomyocytes, aggravating LPS-induced septic cardiomyopathy; DUSP1 overexpression inhibits ANGPTL2-mediated NLRP3 activation and improves cardiac dysfunction. Cardiac ANGPTL2 overexpression/knockdown (AAV vectors), NLRP3 knockdown, DUSP1 overexpression, LPS-induced cardiomyopathy model, echocardiography, pathway analysis International immunopharmacology Medium 37531825
2022 HIF1A transcriptionally activates ANGPTL2 expression (confirmed by luciferase reporter and ChIP assay); ANGPTL2 positively modulates HIF1A expression in cardiomyocytes; ANGPTL2 knockdown activates the Nrf2/HO-1 pathway to protect against hypoxia/reoxygenation injury. Luciferase reporter assay, ChIP assay, ANGPTL2 knockdown/overexpression in H9c2 cells, HIF1A knockdown, Nrf2/HO-1 pathway analysis Bioengineered Medium 34974813
2021 CSN5 (COP9 signalosome subunit 5) directly binds ANGPTL2 protein, decreasing its ubiquitination and proteasomal degradation, thereby elevating ANGPTL2 protein levels in thyroid carcinoma cells. Co-immunoprecipitation, ubiquitination assay, CSN5 gain/loss of function, western blotting for ANGPTL2 protein levels, correlation analysis in patient tissues Endocrinology Medium 33508120
2020 Stroma-derived ANGPTL2 drives generation of immunostimulatory macrophages via the NF-κB pathway, accelerating CD4+ T helper 1 cell activation and enhancing anti-tumor immune responses in intestinal tumorigenesis. ANGPTL2-deficient mice in colitis-associated colon cancer model, immune cell profiling, NF-κB pathway analysis, CD4+ and CD8+ T cell response measurement Oncogene Medium 33051596
2016 ANGPTL2 deficiency in lung epithelial cells and resident alveolar macrophages (not myeloid cells) causes more severe lung fibrosis following bleomycin treatment, indicating ANGPTL2 from these cell types plays a protective role against fibrosis; bone marrow transplant experiments excluded a myeloid cell contribution. Angptl2 KO mice, bleomycin-induced interstitial pneumonia model, bone marrow transplantation, rabbit monoclonal antibody generation for ANGPTL2 detection American journal of physiology. Lung cellular and molecular physiology Medium 27542805
2018 ANGPTL2 knockdown activates the MEK/ERK/Nrf-1 pathway in kidney cells, increasing autophagy and decreasing renal fibrosis markers; knockdown of MEK/ERK reverses these changes, placing ANGPTL2 upstream of this pathway. ANGPTL2 knockdown in high glucose-stimulated HK-2 cells, MEK/ERK pathway inhibition, western blotting for fibrosis and autophagy markers, in vivo STZ-induced diabetic rat model American journal of translational research Medium 31632523
2024 ANGPTL2 and NOX4 physically interact (co-immunoprecipitation in HEK293 cells); ANGPTL2 represses cardiac NOX4 activity, and ANGPTL2 knockdown upregulates cardiac NOX4, causing increased H2O2 production and left ventricular systolic dysfunction; AAV9-mediated NOX4 knockdown reverses LV dysfunction in ANGPTL2-knockdown mice. Co-immunoprecipitation in HEK293 cells, ANGPTL2 knockdown mice, AAV9-shRNA targeting NOX4, echocardiography, cardiac H2O2 measurement, immunofluorescence Frontiers in physiology Medium 38426206
2022 The fibronectin (FBN) domain at the C-terminus of ANGPTL2 is essential for LILRB2 signaling; membrane-anchored N-terminal ANGPTL2 (Nm-Angptl2) activates LILRB2 more potently than soluble ANGPTL2 and more efficiently expands mouse HSCs ex vivo. LILRB2 reporter activation assay, membrane-anchored ANGPTL2 constructs (C-terminal and N-terminal), HSC transplantation and limiting dilution assay Biochemical and biophysical research communications Medium 35675737
2024 ANGPTL2 knockdown in alveolar macrophages reduces LILRB2 expression, thereby relieving LILRB2-mediated inhibition of TREM2, which enhances autophagy and reduces pyroptosis; TREM2 knockdown reverses the protective effects of ANGPTL2 silencing. ANGPTL2 knockdown in LPS-induced mouse ALI model and MH-S cells, LILRB2 overexpression rescue, TREM2 knockdown, autophagy flux detection, pyroptosis markers, western blot Journal of cellular and molecular medicine Medium 38758159
2025 Adipocyte-secreted ANGPTL2 promotes hyperuricemia by inhibiting AKT/ABCG2 signaling in renal tubular cells, reducing uric acid excretion; Angptl2 knockout mice show decreased plasma uric acid and upregulated ABCG2, while adipocyte-specific ANGPTL2 overexpression increases plasma uric acid with decreased ABCG2. Angptl2 knockout mice, adipocyte-specific ANGPTL2 overexpression mice, HK-2 cells and primary RTECs treated with recombinant ANGPTL2, AKT/ABCG2 pathway analysis, DIA proteomics of human adipose tissue Free radical biology & medicine Medium 40180020
2016 DNA methylation of specific CpGs in the ANGPTL2 promoter inhibits ANGPTL2 promoter activity, as demonstrated by in vitro luciferase assay; lower methylation in leukocytes is associated with higher ANGPTL2 expression in post-ACS patients. In vitro luciferase reporter assay with methylated DNA, bisulfite pyrosequencing of ANGPTL2 promoter CpGs, CRP and ANGPTL2 circulating level measurement PloS one Medium 27101308
2021 ANGPTL2 induces MYELOID-derived suppressor cell (MDSC) generation in bone marrow by promoting pro-inflammatory cytokine production in adipose tissue, contributing to an immunosuppressive tumor microenvironment and resistance to ICI therapy in obese mice. Systemic ANGPTL2-deficient mice in syngeneic colorectal cancer model, high-fat diet obesity model, MDSC quantification in bone marrow, cytokine profiling in adipose tissue Cancer science Medium 39321028

Source papers

Stage 0 corpus · 72 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Diverse roles of ANGPTL2 in physiology and pathophysiology. Trends in endocrinology and metabolism: TEM 138 24746520
2014 Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression. Arteriosclerosis, thrombosis, and vascular biology 133 24526691
2012 Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis. Cancer research 116 22345152
2014 The secreted protein ANGPTL2 promotes metastasis of osteosarcoma cells through integrin α5β1, p38 MAPK, and matrix metalloproteinases. Science signaling 108 24448647
2014 A motif in LILRB2 critical for Angptl2 binding and activation. Blood 87 24899623
2013 Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury. Journal of molecular and cellular cardiology 71 23333801
2016 ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism. Nature communications 61 27677409
2023 ANGPTL2+cancer-associated fibroblasts and SPP1+macrophages are metastasis accelerators of colorectal cancer. Frontiers in immunology 59 37691929
2015 ANGPTL2/LILRB2 signaling promotes the propagation of lung cancer cells. Oncotarget 56 26056041
2015 ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling. Scientific reports 55 25773070
2017 ANGPTL2 expression in the intestinal stem cell niche controls epithelial regeneration and homeostasis. The EMBO journal 54 28043948
2015 Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance. PloS one 42 26132105
2021 CD146 is a Novel ANGPTL2 Receptor that Promotes Obesity by Manipulating Lipid Metabolism and Energy Expenditure. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 40 33747748
2021 Tumor-derived miR-378a-3p-containing extracellular vesicles promote osteolysis by activating the Dyrk1a/Nfatc1/Angptl2 axis for bone metastasis. Cancer letters 40 34801597
2017 High Circulating Levels of ANGPTL2: Beyond a Clinical Marker of Systemic Inflammation. Oxidative medicine and cellular longevity 38 29138671
2021 ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression. The Journal of clinical investigation 35 33108353
2019 ANGPTL2 regulates autophagy through the MEK/ERK/Nrf-1 pathway and affects the progression of renal fibrosis in diabetic nephropathy. American journal of translational research 35 31632523
2014 Serum ANGPTL2 levels reflect clinical features of breast cancer patients: implications for the pathogenesis of breast cancer metastasis. The International journal of biological markers 35 24585434
2015 ANGPTL2 promotes tumor metastasis in hepatocellular carcinoma. Journal of gastroenterology and hepatology 31 25090954
2020 Anti-inflammatory activity of berberine in non-alcoholic fatty liver disease via the Angptl2 pathway. BMC immunology 30 32429849
2015 GDC-0152 attenuates the malignant progression of osteosarcoma promoted by ANGPTL2 via PI3K/AKT but not p38MAPK signaling pathway. International journal of oncology 28 25651778
2007 Enhanced expression of ANGPTL2 in the microvascular lesions of diabetic glomerulopathy. Nephron. Experimental nephrology 27 17347581
2020 Myositis ossificans-like soft tissue aneurysmal bone cyst: a clinical, radiological, and pathological study of seven cases with COL1A1-USP6 fusion and a novel ANGPTL2-USP6 fusion. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26 32157177
2018 Angptl2 deficiency attenuates paraquat (PQ)-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis through NF-κB pathway. Biochemical and biophysical research communications 26 29852175
2019 ANGPTL2 Promotes Inflammation via Integrin α5β1 in Chondrocytes. Cartilage 24 31581797
2017 ANGPTL2　- A New Causal Player in Accelerating Heart Disease Development in the Aging. Circulation journal : official journal of the Japanese Circulation Society 24 28867689
2013 Serum Angptl2 levels are independently associated with albuminuria in type 2 diabetes. Diabetes research and clinical practice 24 23602322
2018 Enhanced ANGPTL2 expression in adipose tissues and its association with insulin resistance in obese women. Scientific reports 22 30228336
2021 Angptl2 is a Marker of Cellular Senescence: The Physiological and Pathophysiological Impact of Angptl2-Related Senescence. International journal of molecular sciences 21 34830112
2016 Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients. PloS one 19 27101308
2017 Circulating ANGPTL2 Levels Increase in Humans and Mice Exhibiting Cardiac Dysfunction. Circulation journal : official journal of the Japanese Circulation Society 18 28890470
2023 ANGPTL2 promotes immune checkpoint inhibitor-related murine autoimmune myocarditis. Communications biology 17 37736764
2021 ANGPTL2 Induces Synovial Inflammation via LILRB2. Inflammation 17 33538932
2020 Foxc2 Alleviates Ox-LDL-Induced Lipid Accumulation, Inflammation, and Apoptosis of Macrophage via Regulating the Expression of Angptl2. Inflammation 17 32170602
2018 ANGPTL2 deletion inhibits osteoclast generation by modulating NF-κB/MAPKs/Cyclin pathways. Biochemical and biophysical research communications 17 30031603
2016 Interstitial pneumonia induced by bleomycin treatment is exacerbated in Angptl2-deficient mice. American journal of physiology. Lung cellular and molecular physiology 17 27542805
2023 ANGPTL2 promotes VEGF-A synthesis in human lung cancer and facilitates lymphangiogenesis. Aging 15 36917086
2019 Expression of ANGPTL2 and its impact on papillary thyroid cancer. Cancer cell international 14 31384179
2016 Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity. The Journal of biological chemistry 14 27402837
2020 Stroma-derived ANGPTL2 establishes an anti-tumor microenvironment during intestinal tumorigenesis. Oncogene 13 33051596
2023 ANGPTL2 aggravates LPS-induced septic cardiomyopathy via NLRP3-mediated inflammasome in a DUSP1-dependent pathway. International immunopharmacology 11 37531825
2022 Knockdown of hypoxia-inducible factor 1-alpha (HIF1α) interferes with angiopoietin-like protein 2 (ANGPTL2) to attenuate high glucose-triggered hypoxia/reoxygenation injury in cardiomyocytes. Bioengineered 11 34974813
2021 CSN5 Promotes Carcinogenesis of Thyroid Carcinoma Cells Through ANGPTL2. Endocrinology 11 33508120
2020 Knockdown of ANGPTL2 Protects Renal Tubular Epithelial Cells Against Hypoxia/Reoxygenation-Induced Injury via Suppressing TLR4/NF-κB Signaling Pathway and Activating Nrf2/HO-1 Signaling Pathway. Cell transplantation 11 32993399
2022 Tumor cell-derived ANGPTL2 promotes β-catenin-driven intestinal tumorigenesis. Oncogene 10 35831580
2021 Protective Effect of Irbesartan by Inhibiting ANGPTL2 Expression in Diabetic Kidney Disease. Current medical science 10 33263178
2021 Evaluation of serum Angiopoietin-like protein 2 (ANGPTL-2), Angiopoietin-like protein 8 (ANGPTL-8), and high-sensitivity C-reactive protein (hs-CRP) levels in patients with gestational diabetes mellitus and normoglycemic pregnant women. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10 33615956
2021 Angptl2 gene knockdown is critical for abolishing angiotensin II-induced vascular smooth muscle cell proliferation and migration. Biochemistry and cell biology = Biochimie et biologie cellulaire 9 34860608
2024 ANGPTL2 knockdown induces autophagy to relieve alveolar macrophage pyroptosis by reducing LILRB2-mediated inhibition of TREM2. Journal of cellular and molecular medicine 8 38758159
2023 ANGPTL2-mediated epigenetic repression of MHC-I in tumor cells accelerates tumor immune evasion. Molecular oncology 8 37452654
2016 ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior. World journal of gastroenterology 8 28058016
2023 ANGPTL2 binds MAG to efficiently enhance oligodendrocyte differentiation. Cell & bioscience 7 36855057
2021 Circulating Exosomal miR-221 from Maternal Obesity Inhibits Angiogenesis via Targeting Angptl2. International journal of molecular sciences 7 34638684
2024 Decreased Memory and Learning Ability Mediated by Bmal1/M1 Macrophages/Angptl2/Inflammatory Cytokine Pathway in Mice Exposed to Long-Term Blue Light Irradiation. Current issues in molecular biology 6 38785563
2023 ANGPTL2 Deletion Attenuates Neuroinflammation and Cognitive Dysfunction Induced by Isoflurane in Aged Mice through Modulating MAPK Pathway. Mediators of inflammation 6 36865085
2018 Preliminary study of the relationship between promoter methylation of the ANGPTL2 gene and coronary heart disease. Journal of clinical laboratory analysis 6 30461060
2024 Tumor stroma-derived ANGPTL2 potentiates immune checkpoint inhibitor efficacy. Cancer gene therapy 5 38467764
2022 Efficient expansion of mouse hematopoietic stem cells ex vivo by membrane anchored Angptl2. Biochemical and biophysical research communications 5 35675737
2022 miR-124-3p Combined with ANGPTL2 Has High Diagnostic Values for Obese and Nonobese Polycystic Ovary Syndrome. International journal of endocrinology 5 35747760
2021 Higher levels of circulating ANGPTL2 are associated with macular edema in patients with type 2 diabetes. Medicine 5 33578584
2021 Blocking angiotensin 2 receptor attenuates diabetic nephropathy via mitigating ANGPTL2/TL4/NF-κB expression. Molecular biology reports 5 34431038
2024 Host ANGPTL2 establishes an immunosuppressive tumor microenvironment and resistance to immune checkpoint therapy. Cancer science 4 39321028
2014 Unveiling Angptl2, a rising HSC expander. Blood 4 25104862
2025 A novel photosensitive nanoprobe combined with CRISPR/Cas12a for dual signal amplification detection of ANGPTL2. Talanta 3 40147084
2022 ANGPTL2 aggravates doxorubicin-induced cardiotoxicity via inhibiting DUSP1 pathway. Bioscience, biotechnology, and biochemistry 3 36107816
2026 Context-Dependent Roles of ANGPTL2-Mediated Inflammaging in Tissue Homeostasis, Pathological Tissue Remodeling, and Longevity. Aging cell 2 41508557
2024 Knockdown of ANGPTL2 promotes left ventricular systolic dysfunction by upregulation of NOX4 in mice. Frontiers in physiology 2 38426206
2025 Adipocyte-secreted ANGPTL2 promotes hyperuricemia through inhibiting AKT/ABCG2 signaling. Free radical biology & medicine 1 40180020
2018 Use of ANGPTL2 mRNA levels in formalin-fixed paraffin-embedded tissues as a biomarker to diagnose gastric cancer and to evaluate the extent of vascular invasion. Oncology letters 1 30655796
2011 [Roles of angiopoietin-like protein 2 (Angptl2) in chronic inflammation and atherosclerotic diseases]. Nihon rinsho. Japanese journal of clinical medicine 1 21226278
2025 Serum Angptl2 and CyPA Levels in Acute Myocardial Infarction and In-Stent Restenosis After Percutaneous Coronary Intervention: A Single-Center Retrospective Case-Control Study. Vascular health and risk management 0 40196450
2025 [Retracted] GDC‑0152 attenuates the malignant progression of osteosarcoma promoted by ANGPTL2 via PI3K/AKT but not p38MAPK signaling pathway. International journal of oncology 0 41347835

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