| 1989 |
VCAM-1 was cloned as a novel cytokine-induced endothelial adhesion molecule that binds lymphocytes; it is a member of the immunoglobulin gene superfamily induced by IL-1 or TNF-alpha on human endothelial cells, mediating binding of mononuclear leukocytes but not neutrophils. |
Expression cloning by adhesion selection, transfection, mRNA induction assays |
Cell |
High |
2688898
|
| 1991 |
The human VCAM1 gene contains 9 exons spanning ~25 kb; alternative splicing of exon 5 produces two VCAM-1 precursors (6-domain and 7-domain forms). The promoter contains functional NF-κB, GATA, and AP1 binding sites. |
Genomic cloning, Southern blotting, chromosomal mapping (human-mouse hybrid cell lines and in situ hybridization), mRNA splicing analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
1715583
|
| 1991 |
VCAM-1 binds B cell precursors to bone marrow fibroblasts via the integrin VLA-4 (CD49d/CD29); anti-VCAM-1 antibody blocked adhesion of normal B cell precursors, establishing the VLA-4/VCAM-1 axis in B cell precursor retention in bone marrow. |
Antibody blocking adhesion assays, flow cytometry, co-culture of B cell precursors with bone marrow fibroblasts |
The Journal of clinical investigation |
High |
1715889
|
| 1991 |
A seven-domain (long) form of human VCAM-1 was cloned; both six-domain and seven-domain forms support adhesion of VLA-4-expressing cell lines, with the long form being the major form expressed on endothelium. |
cDNA cloning, immunoprecipitation with deglycosylation, transfection of COS7 cells, adhesion assay |
The Journal of biological chemistry |
High |
1707873
|
| 1992 |
The VCAM-1 promoter is activated by TNF-alpha through two functional NF-κB sites at positions -77 and -63 bp; silencer elements between -1.641 kb and -288 bp restrict constitutive activity; NF-κB responsiveness is cell-type specific (present in endothelial cells but not Jurkat T cells). |
Deletion reporter (CAT) constructs transfected into bovine aortic endothelial cells, EMSA (gel retardation assays), TNF-alpha stimulation |
The Journal of biological chemistry |
High |
1379595
|
| 1992 |
Functional NF-κB and GATA elements in the VCAM-1 core promoter are required for TNF-induced transcription in endothelial cells; new transcription (not mRNA stabilization) drives cytokine-induced VCAM-1 expression. |
Deletion reporter constructs, transfection into bovine aortic endothelial cells, nuclear run-on assays |
The Journal of experimental medicine |
High |
1281211
|
| 1993 |
The murine VCAM1 gene has 10 exons spanning ~20 kb; exon 5 encodes a novel domain unique to murine VCAM-1 and inclusion by alternative splicing produces a truncated three-Ig-domain form anchored by a phosphatidylinositol linkage. The murine and human VCAM1 promoters share conserved NF-κB, Ets, and GATA binding sites. |
Genomic cloning, exon mapping, sequence analysis, alternative splicing characterization |
Genomics |
High |
7507076
|
| 1995 |
Genetic ablation of murine Vcam1 causes failure of allantois-chorion fusion at E8.5, resulting in defective placentation and embryonic lethality, revealing an essential developmental role for VCAM-1 in chorioallantoic fusion. |
Targeted homologous recombination (knockout mice), embryological analysis, histology |
Genes & development |
High |
7530222
|
| 1995 |
Both domain 1 and domain 4 of VCAM-1 independently support VLA-4 (α4β1)-dependent monocyte transendothelial migration; combined blockade of both domains is required for complete inhibition, and their relative contribution depends on the duration of endothelial IL-1 activation. |
Domain-specific anti-VCAM-1 mAb blocking assays, CHO cell transfection with 6-domain and 7-domain VCAM-1 constructs, monocyte migration assays under C5a gradient |
Journal of immunology |
High |
7545712
|
| 1995 |
Membrane-bound VCAM-1 is converted to a soluble 100-kDa form by regulated metalloprotease-dependent proteolytic cleavage; EDTA and 1,10-phenanthroline (metalloprotease inhibitors) block this conversion, and phorbol ester induces shedding with concurrent loss of membrane-bound form. |
Biochemical characterization, metalloprotease inhibitor treatment, phorbol ester stimulation, immunoprecipitation of intracellular precursors and soluble forms in T cell clones |
Journal of immunology |
High |
7529789
|
| 1997 |
TNF-alpha activates p38 MAP kinase in endothelial cells; p38 inhibition (SB203580) suppresses TNF-alpha-induced surface expression of VCAM-1 but not ICAM-1, without affecting VCAM-1 mRNA accumulation, indicating p38 regulates VCAM-1 at the post-transcriptional level. |
p38 MAPK inhibitor (SB203580), MAPKAP kinase 2 activity assays, Hsp27 phosphorylation, flow cytometry for surface expression, Northern blot for mRNA |
Biochemical and biophysical research communications |
Medium |
9020057
|
| 1999 |
α9β1 integrin on neutrophils binds VCAM-1 and mediates stable adhesion and transendothelial neutrophil migration; α9β1 is highly expressed on neutrophils and contributes to chemotaxis across activated endothelium alongside α4 integrins. |
Cell adhesion assays with recombinant VCAM-1, antibody blocking of α9β1, transendothelial migration assays with TNF-alpha-activated HUVEC |
The Journal of cell biology |
High |
10209034
|
| 1999 |
PPARα activators (fenofibrate, WY14643) inhibit TNF-alpha-induced VCAM-1 mRNA expression in human endothelial cells, in part by inhibiting NF-κB activation, and reduce monocyte adhesion; this identifies PPARα as a transcriptional regulator of VCAM-1. |
RT-PCR, transfection with VCAM-1 promoter deletion constructs, EMSA, monocyte adhesion assays, immunohistochemistry |
Circulation |
High |
10377075
|
| 2000 |
VCAM-1 on fibroblast-like synoviocytes (FLS) interacts with CD49d/CD29 (VLA-4) on B cells to rescue synovial B cells from apoptosis and upregulate Bcl-xL expression in a contact-dependent manner; anti-VCAM-1 antibody blocked both effects. |
Co-culture of synovial fluid B cells with FLS, antibody blocking, viability assays (trypan blue, annexin V, Hoechst staining), Western blot for Bcl-xL |
Arthritis and rheumatism |
Medium |
10817566
|
| 2000 |
RA synovial stromal cell VCAM-1 (CD106) interaction with CD49d/CD29 (VLA-4) on B cells induces Bcl-xL upregulation and protects B cells from apoptosis in a contact-dependent manner; anti-CD106 but not anti-CD54 antibody blocked these effects. |
Co-culture with stromal cell lines, antibody blocking, flow cytometry, Bcl-xL/Bcl-2 Western blot |
Journal of immunology |
Medium |
10623863
|
| 2001 |
VCAM-1 expressed by bone marrow stromal cells is proteolytically cleaved by neutrophil serine proteases (neutrophil elastase and cathepsin G) during G-CSF-induced hematopoietic progenitor cell mobilization, enabling HSC egress. |
In vivo mouse mobilization model, immunohistochemistry, in vitro protease cleavage assays with recombinant VCAM-1 and purified neutrophil elastase/cathepsin G |
Blood |
High |
11520773
|
| 2002 |
VCAM-1 interacts directly with moesin and ezrin (ERM proteins) and colocalizes with them at the apical endothelial surface. During leukocyte adhesion, VCAM-1, ICAM-1, activated moesin and ezrin cluster in an endothelial actin-rich docking structure that partially embraces the adherent leukocyte; this structure requires phosphoinositides and the Rho/ROCK pathway. |
In vitro direct binding assay (GST pulldown), live-cell imaging, immunofluorescence, siRNA-mediated knockdown, pharmacological inhibition of Rho/ROCK, dynamic fluorescence microscopy under flow |
The Journal of cell biology |
High |
12082081
|
| 2003 |
PMA-stimulated shedding of VCAM-1 from the cell surface is mediated specifically by TACE (ADAM17), a metalloproteinase that cleaves VCAM-1 near the transmembrane domain to produce soluble VCAM-1; cells from ADAM17-deficient mice lack PMA-induced VCAM-1 shedding. |
Metalloproteinase inhibitors, ADAM17-deficient mouse-derived cells, VCAM-1 shedding assays, comparison with E-selectin/PECAM-1/ICAM-1 shedding |
The Journal of biological chemistry |
High |
12878595
|
| 2006 |
Lymphocyte binding to VCAM-1 activates endothelial cell NADPH oxidase, generating ~1 μM H2O2, which in turn induces oxidation and activation of PKCα (phosphorylation at Thr638); this PKCα activation is required for VCAM-1-dependent leukocyte transendothelial migration. |
Dominant-negative PKCα overexpression, PKCα inhibitors (Rö-32-0432, Gö-6976), H2O2 scavenging, NADPH oxidase inhibition, anti-VCAM-1 antibody cross-linking, PKCα oxidation assay, spleen cell migration under laminar flow |
Journal of immunology |
High |
17056569
|
| 2008 |
miR-126 is expressed by endothelial cells and inhibits VCAM-1 expression; reduction of miR-126 increases TNF-alpha-stimulated VCAM-1 expression and enhances leukocyte adherence, while overexpression of miR-126 precursor decreases VCAM-1 levels. |
Transfection of endothelial cells with miR-126 inhibitor or precursor oligonucleotides, VCAM-1 protein/mRNA quantification, leukocyte adhesion assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
18227515
|
| 2011 |
VCAM-1 aberrantly expressed on breast cancer cells tethers macrophages via α4-integrins; clustering of cancer cell surface VCAM-1, acting through Ezrin, activates PI3K/Akt signaling and protects cancer cells from TRAIL-induced apoptosis in leukocyte-rich microenvironments such as the lung. |
Co-culture of breast cancer cells with macrophages, antibody blocking of α4-integrins, dominant-negative Ezrin, Akt activation assays, TRAIL apoptosis assay, in vivo lung metastasis mouse model |
Cancer cell |
High |
22014578
|
| 2011 |
Aberrant VCAM-1 expression on breast cancer micrometastases in bone promotes transition from dormancy to overt metastasis by recruiting α4β1-positive monocytic osteoclast progenitors via VCAM-1/α4β1 interaction, elevating local osteoclast activity; anti-VCAM-1 and anti-α4 antibodies inhibit this process. |
Bone metastasis dormancy mouse model, NF-κB pathway manipulation, VCAM-1 overexpression, antibody blockade, osteoclast activity assays, in vivo imaging |
Cancer cell |
High |
22137794
|
| 2012 |
IRF-1 and miR-126 reciprocally regulate VCAM-1 expression in response to triglyceride-rich lipoproteins (TGRL): proatherogenic TGRL increase IRF-1 and decrease miR-126, inducing VCAM-1; antiatherogenic TGRL do the opposite. Overexpression or silencing of IRF-1 or miR-126 recapitulates these effects. |
HAEC transfection with IRF-1 overexpression/silencing and miR-126 overexpression/silencing, VCAM-1 expression assay, monocyte arrest assay |
Circulation research |
Medium |
22874466
|
| 2012 |
Nuclear-localized FAK (kinase-inhibited) binds GATA4 transcription factor via its FERM domain, promoting CHIP E3 ligase-dependent polyubiquitination and degradation of GATA4; loss of GATA4 reduces VCAM-1 expression. Active FAK facilitates TNF-α-induced MAPK activation and GATA4 stability, thereby supporting VCAM-1 expression. |
Pharmacological FAK inhibition, conditional endothelial FAK knockout mice, nuclear fractionation, direct FAK-GATA4 binding assay, CHIP co-immunoprecipitation, GATA4 ubiquitination assay, in vivo heart vessel analysis |
The Journal of cell biology |
High |
22734001
|
| 2013 |
Metastatic tumor cell attachment induces endothelial VCAM-1 (dependent on tumor cell-clot/tissue factor formation); endothelial VCAM-1 recruits myeloid cells that support tumor cell survival and metastasis; VCAM-1 blocking antibody reduces myeloid recruitment and diminishes metastasis without affecting tumor cell adhesion. |
In vivo pulmonary metastasis mouse model, VCAM-1 blocking antibody, tissue factor pathway inhibitor/hirudin treatment, flow cytometry for myeloid cells, tumor cell survival assays |
Blood |
Medium |
23407548
|
| 2014 |
VLA-4 (α4β1) on leukocytes interacts with VCAM-1 to mediate reciprocal NF-κB activation in both leukemia cells and bone marrow mesenchymal stromal cells; this bidirectional signaling promotes stromal-mediated chemoresistance, reversible by VLA-4/VCAM-1 blockade or NF-κB inhibition. |
Genome-wide gene expression profiling of BM-MSCs, co-culture, NF-κB reporter assays, mutant IκBα overexpression, VLA-4 blocking antibody, in vivo human leukemia BM microenvironment model |
Blood |
High |
24599548
|
| 2015 |
Tumor-derived SPARC induces endothelial vascular permeability and cancer cell extravasation through VCAM-1 and p38 MAPK signaling; blocking VCAM-1 impedes SPARC-induced permeability and extravasation. |
Comparative proteomic analysis of melanoma secretomes, SPARC knockdown/overexpression, VCAM-1 blocking antibody, vascular permeability assays, lung metastasis mouse model |
Nature communications |
Medium |
25925867
|
| 2015 |
VCAM-1 is a TGF-β1-inducible gene in lung fibroblasts (via transcriptional induction, not mRNA stabilization); VCAM-1 depletion inhibits fibroblast proliferation, causing G2/M and S phase arrest associated with reduced phospho-ERK1/2 and cyclin D1. |
TGF-β1 treatment, VCAM-1 siRNA depletion, mRNA stability assays, cell cycle analysis, Western blot for phospho-ERK1/2 and cyclin D1 |
Cellular signalling |
Medium |
26386411
|
| 2016 |
oxLDL induces NF-κB activation and VCAM-1 expression through FAK-dependent activation of RSK (p90 ribosomal S6 kinase), which activates IKKβ; transgenic mice with endothelial-specific kinase-dead FAK show reduced RSK activity, decreased VCAM-1 expression, and reduced macrophage accumulation in atherosclerotic regions. |
RSK inhibitors, FAK kinase-dead transgenic mice, IKKβ activation assays, NF-κB reporter, monocyte adhesion assay, atherosclerosis model |
Journal of cell science |
High |
26906414
|
| 2017 |
VCAM-1 expression in glioblastoma depends on EGFR expression, and is regulated via the p38/STAT3 signaling pathway; miR-181b, via protein phosphatase 2A-modulated SP-1 dephosphorylation, controls EGFR-dependent VCAM-1 expression and thereby monocyte adhesion to GBM cells through integrin α4β1. |
EGFR inhibition, VCAM-1 knockdown, integrin α4β1 blocking, miR-181b overexpression/inhibition, PP2A assay, SP-1 phosphorylation Western blot, 2D/3D co-culture adhesion assays |
Oncogene |
Medium |
28459461
|
| 2017 |
VCAM-1 signals through its intracellular domain to regulate β-catenin signaling in embryonic radial glial cells (RGCs) in a context-dependent manner; loss of VCAM-1 in RGCs stimulates premature neuronal differentiation and prevents quiescence, depleting the embryonic origin of postnatal neural stem cells. |
Conditional Vcam1 knockout mice (region- and stage-specific), β-catenin reporter assays, BrdU labeling, clonal analysis, in vitro neural stem cell assays |
Neuron |
High |
28728023
|
| 2017 |
VCAM-1 synergizes with Delta-like 4 (DLL4) to enhance Notch signaling in hematopoietic stem and progenitor cells and promote T-lineage differentiation; VCAM-1 additionally activates an inflammatory transcriptional program in nascent HSPCs. |
Defined stromal cell-free in vitro T cell differentiation system, DLL4/VCAM-1 protein presentation on surfaces, Notch reporter assays, flow cytometry for T cell progenitors, in vivo thymus colonization |
Nature methods |
Medium |
28394335
|
| 2018 |
VCAM-1+ macrophage-like 'usher' cells patrol the inner surface of the venous plexus in zebrafish caudal haematopoietic tissue, interact with HSPCs via ITGA4, and direct HSPC retention at vascular homing hotspots. |
Advanced live imaging in zebrafish, cell-labelling system, ITGA4 blocking, in vivo loss-of-function |
Nature |
High |
30455424
|
| 2019 |
Brain endothelial VCAM-1 mediates the detrimental effects of aged plasma on young brains: aged plasma elevates VCAM-1 on BECs; anti-VCAM-1 antibody administration or genetic ablation of Vcam1 in BECs counteracts microglial reactivity and cognitive deficits induced by aged plasma in young mice. |
Systemic anti-VCAM-1 antibody, conditional endothelial Vcam1 KO mice, parabiosis/plasma transfer model, microglial activation assays, cognitive behavioral tests |
Nature medicine |
High |
31086348
|
| 2021 |
M2 macrophage VLA-4 (α4β1) engagement with endothelial VCAM-1 induces vascular permeability through a RAC1/ROS/PYK2 phosphorylation/VE-cadherin phosphorylation cascade; downregulation of VLA-4 or VCAM-1 reduces RAC1 and ROS, decreases p-PYK2 and p-VE-cadherin, and enhances barrier integrity. Targeting the VLA-4/VCAM-1 axis abrogates ascites formation in vivo. |
VLA-4 overexpression/knockdown, VCAM-1 overexpression in ECs, RAC1/ROS/PYK2/VE-cadherin signaling assays, vascular permeability assay, in vivo ovarian cancer ascites model |
The Journal of clinical investigation |
High |
33295887
|
| 2021 |
HDAC1/2 promote endothelial VCAM-1 expression by suppressing STAT3 acetylation-dependent methylation (via DNMT1) of the GATA6 promoter; HDAC1/2 inhibition increases STAT3 acetylation, promotes STAT3-DNMT1 interaction, leads to GATA6 promoter hypermethylation, reduces GATA6 and VCAM-1 expression, and attenuates atherosclerosis. |
HDAC1/2 siRNA, Romidepsin treatment, methylation-specific PCR, ChIP for STAT3 at GATA6 promoter, STAT3 Lys685Arg acetylation-blocking mutant, DNMT1 co-immunoprecipitation, ApoE-/- mouse atherosclerosis model |
Theranostics |
High |
33859766
|
| 2022 |
VCAM-1 on haematopoietic stem cells serves as a 'don't-eat-me' signal providing innate immune tolerance; this function is regulated by β2-microglobulin/MHC-I presentation on HSCs and paired Ig-like receptor-B (PIR-B) on phagocytes. VCAM-1 deletion in haplotype-mismatched settings impairs HSC engraftment due to phagocytic clearance. |
Vcam1 conditional KO, haplotype-mismatch transplantation, MHC-I/β2m blocking, PIR-B KO phagocytes, phagocytosis assays, in vivo HSC engraftment assays |
Nature cell biology |
High |
35210567
|
| 2022 |
DLL4 and VCAM-1 synergize to activate Notch signaling in nascent HSPCs during endothelial-to-haematopoietic transition, enhancing T cell progenitor output ~80-fold; VCAM-1 additionally promotes an inflammatory transcriptional program in HSPCs. |
Defined serum/feeder-free PSC differentiation system, single-protein presentation, Notch reporter, transcriptomic analysis, flow cytometry, in vivo T cell maturation |
Science advances |
Medium |
36001668
|
| 2023 |
IL-33 induces VCAM-1 in microglia, which promotes microglial chemotaxis toward amyloid-β plaques by sensing plaque-associated ApoE; disrupting the VCAM-1-ApoE interaction abolishes microglial Aβ chemotaxis and decreases Aβ clearance. |
IL-33 stimulation of microglia, VCAM-1 functional screening, VCAM-1-ApoE interaction blocking, Aβ chemotaxis assays, in vivo Alzheimer's disease mouse model |
Nature aging |
Medium |
37735240
|
| 2021 |
Membrane-bound SCF and VCAM-1 synergistically regulate HSC morphology: HSCs cluster membrane-bound SCF at the HSC-bilayer interface and form a polarized morphology with large protrusion; VCAM-1 dramatically enhances HSC adhesion to the bilayer through a mechanism requiring PI3K signaling and cytoskeletal reorganization, and the synergy enhances nuclear retention of FOXO3a. |
Supported lipid bilayer reconstitution system, PI3K inhibitors, cytoskeletal disruption, FOXO3a localization by immunofluorescence, HSC adhesion force measurements |
The Journal of cell biology |
Medium |
34402812
|
| 2015 |
Notch1 intracellular domain (N1ICD) in endothelial cells upregulates Jagged1 and directly induces VCAM-1 expression in the absence of inflammatory cytokines; Notch1/Jagged1 circuit amplifies IL-1β-induced VCAM-1 induction. γ-Secretase inhibition and Notch1/Jagged1 silencing abrogate IL-1β-mediated VCAM-1 induction. |
γ-Secretase inhibitor, Notch1/Jagged1 siRNA silencing, forced N1ICD expression, VCAM-1 quantification, in vivo chronic liver inflammation model |
Oncotarget |
Medium |
26646450
|
| 2020 |
H. pylori infection increases VCAM-1 expression in cancer-associated fibroblasts via JAK/STAT1 signaling; CAF-derived VCAM-1 physically interacts with integrin αvβ1/5 on gastric cancer cells to facilitate tumor invasion in vitro and in vivo. |
RNA-seq of H. pylori-infected fibroblasts, JAK/STAT1 inhibitors, biolayer interferometry for VCAM1-integrin binding kinetics, zebrafish xenograft invasion model |
Oncogene |
Medium |
32034307
|
| 2024 |
H3K18 lactylation in the gastric cancer tumor microenvironment transcriptionally activates VCAM-1; VCAM-1 in turn activates AKT-mTOR signaling to promote GC cell proliferation and migration, and upregulates CXCL1 via AKT-mTOR to recruit mesenchymal stem cells and M2 macrophages. |
H3K18 lactylation ChIP, VCAM-1 overexpression/knockdown, AKT-mTOR pathway inhibitors, CXCL1 quantification, macrophage/MSC recruitment assays, GC mouse models |
Biochemical pharmacology |
Medium |
38461905
|
| 2024 |
Proinflammatory cytokines (TNF-α and IL-1β) induce NF-κB-dependent VCAM-1 expression in proximal tubule cells; tubular VCAM-1 overexpression or TNF-α stimulation increases splenocyte adhesion to tubular monolayers; pharmacological NF-κB inhibition or genetic Vcam1 deletion suppresses this tubule-immune cell adhesion. |
TNF-α/IL-1β treatment of immortalized mouse proximal tubular cells and primary renal cells, NF-κB inhibitors, MyD88/TRIF double-KO cells, VCAM-1 overexpression, splenocyte adhesion assay, single-cell transcriptomics of patient biopsies |
American journal of physiology. Renal physiology |
Medium |
39116349
|
| 2022 |
VCAM-1-bearing endothelial cell-derived extracellular vesicles (EVs) are rapidly released after myocardial infarction and accumulate in the spleen, where they induce inflammatory gene expression and mobilize splenic neutrophils to peripheral blood; CRISPR/Cas9 deletion of VCAM-1 in endothelial cells removes the ability of EVs to provoke neutrophil mobilization. |
CRISPR/Cas9 VCAM-1-deficient endothelial cells, EV characterization (size/marker), in vivo splenic neutrophil mobilization assay, miRNA-126 in vivo inhibition, MI mouse model |
Cardiovascular research |
Medium |
35134856
|