Affinage

ITGA1

Integrin alpha-1 · UniProt P56199

Length
1179 aa
Mass
130.8 kDa
Annotated
2026-04-28
89 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITGA1 encodes the α1 subunit of the collagen- and laminin-binding integrin α1β1 (VLA-1/CD49a), a heterodimeric receptor that mediates divalent-cation-dependent (Mg²⁺/Mn²⁺-supported, Ca²⁺-inhibited), RGD-independent adhesion to collagens I–IV and laminin, coupling extracellular matrix engagement to intracellular FAK-ERK and STAT3 signaling (PMID:2229189, PMID:1807406, PMID:37293163, PMID:40939856). In the immune system, α1β1 is essential for tissue retention, locomotion, and effector function of memory/resident T cells and NK cells in non-lymphoid organs, and it sustains MDSC–T cell suppressive contacts on collagen IV substrates (PMID:14975239, PMID:20200271, PMID:32439709, PMID:33584706). ITGA1 transcription is controlled by CpG promoter methylation, SRF/CArG-box binding, and the transcription factors E2F1, TEAD1, RUNX2/RUNX3, and GTF2B, with KDM4C-mediated H3K9me3 demethylation providing an additional epigenetic layer (PMID:17669516, PMID:28264467, PMID:37269830, PMID:38169150, PMID:40778546). In cartilage, α1β1 normally dampens TGFβR2 signaling to protect against osteoarthritis, as demonstrated by genetic epistasis in Itga1-null mice (PMID:37649532).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1985 High

    Establishing that VLA-1 is a heterodimer of distinct α1 (~210 kDa) and β1 (~130 kDa) glycoprotein subunits resolved the molecular identity of what would become the founding collagen-binding integrin.

    Evidence Immunoprecipitation, chemical cross-linking, glycosidase digestion, and peptide mapping of VLA-1 from human T cell lines

    PMID:2415516

    Open questions at the time
    • No ligand identified at this stage
    • Post-translational modification details beyond glycosylation unknown
  2. 1991 High

    Defining VLA-1's ligand specificity — collagens I–IV and laminin via a Ca²⁺/Mg²⁺-dependent, non-RGD mechanism — distinguished it from RGD-binding integrins and established the biochemical basis for its adhesive function.

    Evidence Purified VLA-1 reconstituted into liposomes tested for binding to multiple ECM substrates with peptide inhibition and divalent cation manipulation

    PMID:1807406 PMID:2229189

    Open questions at the time
    • Structural basis for collagen versus laminin selectivity not resolved
    • No crystal structure of the I-domain/collagen interface
  3. 1994 Medium

    Demonstrating that Mg²⁺/Mn²⁺ support and Ca²⁺ inhibits VLA-1-mediated adhesion, and that inside-out activation occurs via β1 stimulatory antibodies, established the regulatory logic of VLA-1 activation in living cells.

    Evidence Cell adhesion assays with divalent cation manipulation and activating/blocking monoclonal antibodies on neuroblastoma and T cell lines

    PMID:7516898 PMID:8025956

    Open questions at the time
    • Intracellular signaling pathways triggered by outside-in VLA-1 engagement not mapped
    • Inside-out activation signals from TCR to VLA-1 undefined
  4. 2000 High

    The first VLA-1-null mouse revealed a non-redundant role for α1β1 in maintaining gut intraepithelial lymphocyte numbers and collagen-dependent T cell proliferation, shifting understanding from a generic adhesion receptor to one with tissue-specific immune functions.

    Evidence Itga1-knockout mouse with flow cytometric enumeration of IELs and in vitro adhesion/proliferation assays

    PMID:10805967

    Open questions at the time
    • Survival versus homing contribution to IEL reduction not distinguished
    • Downstream intracellular signals mediating proliferative support on collagen unknown
  5. 2004 High

    Demonstrating that VLA-1 is required for tissue retention of influenza-specific CD8⁺ memory T cells in the lung — with antibody blockade and KO yielding concordant results — established α1β1 as a master regulator of tissue-resident memory (TRM) positioning.

    Evidence Anti-α1 antibody blockade and Itga1-KO mice challenged with influenza; tissue-specific T cell enumeration and heterosubtypic immunity assay

    PMID:14975239

    Open questions at the time
    • Whether VLA-1 actively signals survival or merely anchors cells not resolved
    • Relative contribution of collagen I versus IV binding to lung retention unclear
  6. 2007 High

    Identification of CpG methylation of 19 sites in the ITGA1 promoter as the epigenetic silencing mechanism during megakaryocyte differentiation, with SRF/CArG-box involvement, revealed how ITGA1 expression is lineage-restricted.

    Evidence Bisulfite sequencing, promoter-luciferase reporter, and 5-aza-2′-deoxycytidine demethylation rescue in megakaryocytic cells

    PMID:17669516

    Open questions at the time
    • Which DNA methyltransferases target the ITGA1 promoter not identified
    • Whether methylation-based silencing operates in lymphocyte subsets unknown
  7. 2010 High

    Extending the TRM paradigm to CD4⁺ T cells, α1-null mice showed that VLA-1 is required for airway CD4⁺ memory accumulation and rapid IFN-γ recall, broadening its role beyond CD8⁺ TRM.

    Evidence Itga1-KO mice after influenza infection; airway and lymphoid tissue T cell enumeration, intracellular cytokine staining, apoptosis marker analysis

    PMID:20200271

    Open questions at the time
    • Whether VLA-1 provides a direct anti-apoptotic signal in CD4⁺ TRM not mechanistically defined
  8. 2017 Medium

    Two discoveries addressed ITGA1's transcriptional control and cancer biology: E2F1 was shown to directly bind and activate the ITGA1 promoter, while ITGA1 was shown to be required for collagen-induced stemness, EMT, and gemcitabine resistance in pancreatic cancer.

    Evidence ChIP and dual-luciferase reporter for E2F1-ITGA1 promoter binding; siRNA/shRNA knockdown of ITGA1 with ALDH1 stem marker, EMT marker, and in vivo metastasis readouts

    PMID:28264467 PMID:28855593

    Open questions at the time
    • Whether E2F1 regulation of ITGA1 operates in non-cancer contexts unknown
    • Direct versus collagen-mediated mechanism of gemcitabine resistance not dissected
  9. 2020 Medium

    Intravital imaging overturned the pure 'anchor' model by showing that VLA-1 facilitates T cell locomotion in tissues rather than immobilizing cells, reframing α1β1 as a motility-enabling receptor for local immune surveillance.

    Evidence In vitro motility assay and intravital two-photon imaging of virus-specific CD8⁺ T cells in lungs after influenza infection

    PMID:32439709

    Open questions at the time
    • Molecular mechanism by which collagen engagement promotes motility not defined
    • Whether motility function is collagen-subtype-specific unknown
  10. 2021 High

    VLA-1-dependent binding to collagen IV was shown to sustain extended MDSC–T cell contacts required for immune suppression, identifying a collagen-subtype-specific function in immunoregulation beyond T cell–intrinsic roles.

    Evidence Itga1-KO MDSCs with intravital two-photon microscopy measuring contact duration and T cell suppression on collagen IV versus fibronectin substrates

    PMID:33584706

    Open questions at the time
    • Whether other collagen-binding integrins compensate for VLA-1 loss on MDSCs not tested
    • Signal transduction within MDSCs downstream of VLA-1 ligation unknown
  11. 2023 High

    Three parallel advances defined new transcriptional regulators and a tissue-protective signaling role: RUNX2/3 were identified as required for IL-15/TGF-β-induced CD49a expression in TRM differentiation; genetic epistasis showed α1β1 normally dampens TGFβR2 signaling to protect cartilage from osteoarthritis; and GTF2B was shown to activate ITGA1 transcription downstream of a lncRNA/m6A axis, coupling ITGA1 to FAK-ERK signaling in pancreatic cancer.

    Evidence RUNX2/3 siRNA with ATAC-seq/RNA-seq in TRM; Itga1-KO × cartilage-specific Tgfbr2-KO double-mutant rescue in OA model; RNA pull-down and ChIP for GTF2B at ITGA1 promoter with FAK/ERK phosphorylation readout

    PMID:37269830 PMID:37293163 PMID:37649532

    Open questions at the time
    • Direct physical mechanism by which α1β1 dampens TGFβR2 not identified
    • Whether RUNX2/3 regulation is specific to epidermal TRM or general to all TRM lineages unknown
  12. 2025 Medium

    Recent work extended ITGA1's roles to neuroinflammation and endothelial senescence: microglial Itga1 drives NLRP3 inflammasome activation via PGAM5 in Parkinson's disease models, ITGA1 signals through STAT3 in retinoblastoma, and KDM4C-mediated H3K9me3 demethylation at the ITGA1 promoter provides an additional epigenetic control layer in endothelial cells.

    Evidence Conditional microglial Itga1 KD with transcriptomics and NLRP3 assembly assay; ITGA1 KD with STAT3 agonist rescue in retinoblastoma; ChIP for H3K9me3 at ITGA1 promoter with KDM4C inhibition in HUVECs

    PMID:40778546 PMID:40939856 PMID:41462565

    Open questions at the time
    • PGAM5 as a direct α1β1 effector versus indirect transcriptional target not resolved
    • Whether STAT3 is a general downstream effector of α1β1 across cell types unknown
    • KDM4C regulation of ITGA1 shown only in endothelial context

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of α1β1's dual collagen/laminin recognition; how α1β1 physically inhibits TGFβR2 signaling at the membrane; the intracellular signaling cascade linking collagen engagement to T cell motility; and whether the diverse downstream pathways (FAK-ERK, STAT3, PGAM5-NLRP3) reflect cell-type-specific rewiring or a shared proximal signaling node.
  • No high-resolution structure of full-length α1β1 in complex with collagen
  • No reconstituted signaling cascade from VLA-1 ligation to TRM motility
  • Interplay between epigenetic regulators (CpG methylation, KDM4C/H3K9me3) and transcription factors (E2F1, RUNX2/3, TEAD1) at the ITGA1 locus not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0031012 extracellular matrix 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3
Partners
E2F1FAKITGB1RUNX2RUNX3SRFSTAT3TEAD1
Complex memberships
α1β1 integrin (VLA-1)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1985 VLA-1 (ITGA1/CD49a) is a heterodimeric cell-surface complex composed of an Mr 210,000 alpha1 subunit in acid-labile association with an Mr 130,000 beta subunit (beta1), as demonstrated by cross-linking and immunoprecipitation experiments. The alpha1 and beta subunits each contain substantial sialic acid and N-linked carbohydrate, and are non-homologous to each other by one-dimensional peptide mapping. Immunoprecipitation, chemical cross-linking, neuraminidase/endoglycosidase F digestion, 1D peptide mapping The Journal of biological chemistry High 2415516
1990 VLA-1 integrin purified from human smooth muscle by collagen-Sepharose affinity chromatography mediates adhesion to type I, II, III, and IV collagens, C1q, and laminin in a Ca2+/Mg2+-dependent manner, but does not bind gelatin, fibronectin, or thrombospondin, establishing the substrate specificity of ITGA1-containing integrin. Affinity chromatography purification, liposome adhesion assay, inhibition with divalent cations, immunoblotting The Journal of cell biology High 2229189
1991 Purified VLA-1 from human smooth muscle interacts via a Ca2+/Mg2+-dependent mechanism with interstitial collagens I, II, and III and basement membrane proteins (collagen IV and laminin) but not with fibronectin, thrombospondin, or albumin; denaturation of collagen I reduces binding 5-7-fold, and GRGDSP peptide does not inhibit binding, indicating a non-RGD-dependent collagen-binding mechanism. Affinity chromatography purification, liposome binding assay, substrate denaturation, peptide inhibition Biokhimiia (Moscow, Russia) High 1807406
1994 VLA-1-mediated adhesion of neuroblastoma NB100 cells to collagen type I is supported by Mg2+ or Mn2+ but not Ca2+ alone; Ca2+ inhibits Mg2+-supported adhesion. VLA-1 can be directly activated by the stimulatory anti-beta1 monoclonal antibody TS2/16, demonstrating inside-out and outside-in regulation of integrin activity. Cell adhesion assay with divalent cation manipulation, blocking and activating monoclonal antibodies, novel blocking anti-alpha1 mAb 5E8D9 FEBS letters Medium 7516898
1994 VLA-1 (CD49a/alpha1beta1) on long-term activated human T lymphocytes functions as a specific collagen IV receptor; antibody blockade of CD49a inhibits adhesion to collagen IV by ~94% and collagen I by ~82%, and ligation of VLA-1 induces spreading on collagen IV in a Mg2+-dependent manner and can signal IL-2 receptor expression in gamma-delta T cells. Radiolabeled adhesion assay, blocking monoclonal antibody (1B3.1), cell spreading morphology, IL-2R induction readout Cellular immunology Medium 8025956
1995 Glomerular epithelial cells use VLA-1 and VLA-2 cooperatively for adhesion to laminin but rely on VLA-2 alone for collagen adhesion, whereas mesangial cells use VLA-1 for laminin adhesion and both VLA-1 and VLA-2 for collagen, demonstrating cell-type-specific modulation of VLA-1 ligand-binding specificity. Blocking monoclonal antibodies against rat VLA-1 and VLA-2, cell adhesion assay to ECM proteins, ELISA and immunocytochemistry Laboratory investigation Medium 7898055
1999 Integrin alpha1beta1 (VLA-1) is the primary collagen receptor on human intestinal intraepithelial lymphocytes (IELs); antibody blockade of both alpha1 (CD49a) and beta1 subunits inhibited adhesion to collagen I by 82% and collagen IV by 94%, and adhesion was dependent on extracellular divalent cations (Mg2+ and Mn2+ supported; Ca2+ inhibited) and upregulated by PKC stimulation. 51Cr-labelled lymphocyte adhesion assay, blocking antibodies, divalent cation manipulation, phorbol ester/staurosporine treatment Immunology Medium 10457223
2000 VLA-1 (integrin alpha1beta1) is required for normal numbers of gut intraepithelial lymphocytes; VLA1-null mice show ~50% reduction in intestinal IELs despite normal peripheral lymphocyte distribution, and IL-2-stimulated VLA1-null splenocytes show deficient adhesion to fibrillar and basement membrane collagen and reduced proliferation on collagen substrate. Genetic knockout mouse (VLA1-null), flow cytometry, adhesion assay, proliferation assay Cellular immunology High 10805967
2002 VLA-1 (alpha1beta1 integrin) mediates both glomerular and interstitial fibrosis in crescentic glomerulonephritis; delayed antibody blockade of VLA-1 reduced glomerular and tubulointerstitial scarring, decreased type IV collagen and ED-A fibronectin deposition, and increased MMP-9 expression in the glomeruli of treated rats. Anti-VLA-1 antibody treatment (Ha31/8) in rat nephrotoxic nephritis model, immunohistochemistry, serum creatinine, Kaplan-Meier renal survival The American journal of pathology Medium 12368200
2003 VLA-1 (alpha1beta1 integrin) expression marks a stable phenotypic subset of human CD4+ memory T cells enriched for Th1 cytokine production; VLA-1+ CD4+ T cells are selectively enriched for recall antigen-responsive cells, and depletion of the small VLA-1+ fraction from CD4+ PBLs significantly abrogated the proliferative response to recall antigens. Flow cytometry, T cell depletion and reconstitution, recall antigen proliferation assay, cytokine polarization The Journal of clinical investigation Medium 14597770
2004 The collagen-binding alpha1beta1 integrin (VLA-1/CD49a) is responsible for retention of influenza-specific CD8 memory T cells in the lung and other nonlymphoid tissues; antibody blockade or genetic deficiency of VLA-1 decreased virus-specific CTL in lung/nonlymphoid tissues and increased them in spleen, and impaired secondary heterosubtypic immunity. Antibody blockade and genetic KO mouse model, flow cytometry of tissue-specific T cells, heterosubtypic challenge model Immunity High 14975239
2007 The ITGA1 promoter contains a CArG box bound by serum response factor (SRF). Selective CpG methylation of a CpG-rich ITGA1 promoter region is the epigenetic mechanism suppressing ITGA1 expression during megakaryocyte differentiation; 5-aza-2'-deoxycytidine (but not trichostatin A) induced de novo ITGA1 expression in megakaryocytic cells, and progressive CpG methylation at 19 CpG sites occurs during thrombopoietin-induced megakaryocyte differentiation. Sodium bisulfite genomic sequencing, promoter-LUC reporter transfection, 5-aza-CdR treatment, mRNA expression analysis Biochimica et biophysica acta High 17669516
2007 CD49a (alpha1beta1) and CD49b (alpha2beta1) show reciprocal expression on CD8 and CD4 T cells in influenza-infected lung, correlating with distinct spatial localizations: CD8+ T cells associate with collagen IV-rich basement membranes of airways/blood vessels, while CD4+ T cells localize in collagen I-rich interstitial spaces. Flow cytometry, immunofluorescent tissue analysis of collagen distribution and T cell localization Journal of immunology Medium 17372009
2010 VLA-1 (CD49a/alpha1beta1) is required for the accumulation and maintenance of a tissue-memory CD4+ T cell population in the airways after influenza infection; alpha1-/- mice showed fewer memory/effector CD4+ T cells in airways (but not lymphoid tissues), and CD49a+ airway CD4+ T cells were enriched for early IFN-gamma secretion upon secondary challenge and showed reduced apoptosis markers. Alpha1-/- knockout mice, flow cytometry, intracellular cytokine staining, apoptosis markers Journal of immunology High 20200271
2014 CD49a promotes T-cell-mediated hepatitis; CD49a-/- mice were protected from ConA-induced hepatitis with significantly reduced serum ALT and decreased IFN-gamma and IL-17A production. CD49a blockade in vivo ameliorated hepatitis with reduced inflammatory cytokine production by CD4+ T and invariant NKT cells. CD49a-/- knockout mouse, ConA-induced hepatitis model, serum ALT, intracellular cytokine staining, in vivo antibody blockade Immunology High 24164540
2017 TGF-beta and IL-12 induce CD49a expression by CD8+ T cells in vitro; CD49a is expressed early following T cell activation in vivo but is not required for generation of a primary CD8+ T cell response to cutaneous HSV infection or migration across epidermal basement membrane. Rather, CD49a supports CD8+ TRM persistence in skin, regulates epidermal TRM dendritic extensions, and increases the frequency of IFN-gamma+ CD8+ TRM following local antigen challenge. In vitro cytokine stimulation, CD49a KO mouse, cutaneous HSV infection model, flow cytometry, intravital imaging of dendritic extensions Cell reports High 32877667
2017 ITGA1 is required for collagen-induced tumorigenic potential in pancreatic ductal adenocarcinoma cells; ITGA1 depletion revealed it promotes survival of ALDH1-positive stem-like cells, cooperates with TGF-beta to drive gemcitabine resistance, and is required for TGF-beta/collagen-induced EMT and metastasis. ITGA1 siRNA/shRNA knockdown, collagen adhesion/invasion assays, ALDH1 stem cell marker analysis, gemcitabine resistance assay, EMT marker western blot, in vivo metastasis model Scientific reports Medium 28855593
2017 E2F1 transcription factor directly upregulates ITGA1 expression; dual luciferase reporter assay and chromatin immunoprecipitation showed E2F1 binds the ITGA1 promoter to activate transcription, and d-ICD treatment inhibits E2F1 expression, thereby reducing ITGA1 levels and suppressing HCC cell migration and invasion. Dual luciferase reporter assay, chromatin immunoprecipitation (ChIP), qRT-PCR, western blot, wound healing and transwell invasion assay International journal of molecular sciences Medium 28264467
2019 CD49a on decidual NK cells regulates their cytotoxic activity, migration, and adhesion; neutralization of CD49a with blocking antibody increased perforin, granzyme B, and IFN-gamma expression, increased killing activity in 51Cr release assay, and decreased migration and adhesion of dNK cells. A newly identified lncRNA (lnc-49a) was identified as a positive regulator of CD49a expression in primary human NK cells. CD49a neutralizing antibody, flow cytometry, 51Cr release cytotoxicity assay, migration and adhesion assay, lncRNA microarray analysis American journal of reproductive immunology Medium 30756436
2020 CD49a (VLA-1) facilitates locomotion of virus-specific CD8 T cells both in vitro and in vivo in the pulmonary system after influenza infection, contrary to an expected pure retention function; CD49a facilitates T cell motility rather than immobilizing cells, potentially contributing to local surveillance. In vitro motility assay, intravital imaging (in vivo), flow cytometry of TRM phenotype development Proceedings of the National Academy of Sciences Medium 32439709
2021 CD49a expression on tumor-infiltrating CD8+ T cells increases their motility in the tumor microenvironment, particularly in proximity to tumor cells, suggesting CD49a may interfere with productive TCR engagement of tumor cells; expression of CD49a was driven by antigen-independent elements in the TME and further increased by TCR stimulation. Live tumor slice imaging of T cell motility, flow cytometry, Nur77 reporter for TCR engagement, short-term CD49a blockade Cancer immunology research Medium 33619119
2021 VLA-1 binding to collagen IV provides the substrate for extended contact times between myeloid-derived suppressor cells (MDSCs) and effector CD4+ T cells required for T cell suppression; Itga1-/- A-MDSCs showed equivalent splenic homing but shorter interaction times with Teff on collagen IV (but not fibronectin) and reduced suppressive capacity, as measured by T cell proliferation inhibition and apoptosis induction. Itga1-/- genetic KO, in vitro suppression assay on collagen IV vs. fibronectin substrate, intravital two-photon microscopy, T cell proliferation and apoptosis assay Frontiers in immunology High 33584706
2023 RUNX2 and RUNX3 transcription factors are required for IL-15/TGF-beta-induced CD49a expression and the cytotoxic transcriptional profile in circulating CD8+ T cells differentiating toward epidermal TRM cells; RUNX-binding motifs are enriched in epidermal CD8+CD103+CD49a+ TRM cells and RUNX2/RUNX3 protein is highly expressed in this population. RUNX2/3 siRNA knockdown, in vitro stimulation with IL-15+TGF-beta, flow cytometry, RNA-seq transcriptional profiling, ATAC-seq motif enrichment, single-cell paired skin/blood clonotype analysis Immunity High 37269830
2023 ITGA1 loss in cartilage increases TGFBR2 signaling, and this enhanced TGFBR2 signaling drives early and more severe knee osteoarthritis in itga1-null mice; cartilage-specific depletion of TGFBR2 in itga1-null mice attenuated OA progression, establishing an epistatic relationship where integrin alpha1beta1 normally dampens TGFBR2 signaling to protect against OA. Itga1-/- global KO mouse, tamoxifen-inducible cartilage-specific TGFBR2 depletion (double-mutant epistasis), histological OA scoring, behavioral pain assessment, longitudinal study Osteoarthritis and cartilage open High 37649532
2023 Linc00662 recruits GTF2B to activate ITGA1 transcription in a m6A-dependent manner; ITGA1 then initiates focal adhesion formation through the ITGA1-FAK-ERK pathway, promoting malignant behavior in pancreatic cancer cells. FAK inhibitor Y15 suppressed tumor progression in Linc00662-overexpressing cells. RNA pull-down, co-IP, ChIP showing GTF2B at ITGA1 promoter, western blot for FAK/ERK phosphorylation, in vitro invasion/migration, in vivo xenograft American journal of cancer research Medium 37293163
2024 TEAD1 is a key transcriptional regulator of ITGA1 (and ITGA2) expression in prostate cancer cells; TEAD1 loss phenocopies dual ITGA1/ITGA2 deletion in promoting EMT via enhanced TGF-beta1 secretion/autocrine activation and nuclear YAP1 targeting. Genomic deletion of both ITGA1 and ITGA2 activates EMT and converts benign prostate epithelial cells into tumorigenic cells in vivo. TEAD1 siRNA knockdown, ITGA1/ITGA2 genomic deletion, genome-wide co-expression analysis, EMT assay, TGF-beta1 ELISA, YAP1 nuclear localization, in vivo tumorigenicity assay Advanced science Medium 38169150
2025 Microglial CD49a (Itga1) drives neuroinflammation in Parkinson's disease models through PGAM5 as a central regulatory node; microglial Itga1 knockdown attenuates hyperreactivity, ameliorates mitochondrial dysfunction, suppresses NLRP3 inflammasome assembly via PGAM5 downregulation, and preserves dopaminergic neurons. The disintegrin polypeptide obtustatin specifically antagonizes microglial CD49a, suppressing neuroinflammation and improving motor deficits. Conditional microglial Itga1 knockdown, transcriptomic profiling of isolated microglia, mitochondrial function assay, NLRP3 inflammasome assembly assay, PD mouse models, obtustatin pharmacological antagonism Advanced science Medium 41462565
2025 ITGA1 knockdown or pharmacological inhibition with obtustatin impairs retinoblastoma cell proliferation, migration, and clonogenicity; STAT3 was identified as a key downstream mediator of ITGA1 signaling, and a STAT3 agonist (ML115) partially rescued the inhibitory effects of ITGA1 suppression. ITGA1 partners with ITGB1 in retinoblastoma cells. Lentiviral ITGA1 knockdown, obtustatin treatment, transcriptome analysis, western blot, STAT3 agonist rescue, in vivo xenograft model Experimental eye research Medium 40939856
2025 Luteolin suppresses ITGA1 transcription in endothelial cells by inhibiting KDM4C-mediated demethylation of H3K9me3 at the ITGA1 promoter; ITGA1 knockdown improved AGEs-induced senescent HUVEC functional impairments (proliferation, migration, tube formation) and reduced senescence markers, while ITGA1 overexpression abrogated luteolin's protective effects. The EGFR/MEK/ERK pathway is downstream of ITGA1 in this context. ITGA1 siRNA knockdown, ITGA1 overexpression, ChIP for H3K9me3 at ITGA1 promoter, KDM4C inhibition, EGFR/MEK/ERK western blot, in vivo diabetic wound model Journal of biochemical and molecular toxicology Medium 40778546

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin. Immunity 548 28214226
2004 The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity 252 14975239
1992 T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1. Arteriosclerosis and thrombosis : a journal of vascular biology 248 1531930
2015 Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells. Journal of immunology (Baltimore, Md. : 1950) 210 25672754
1985 VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. European journal of immunology 159 2986987
1985 Biochemical characterization of VLA-1 and VLA-2. Cell surface heterodimers on activated T cells. The Journal of biological chemistry 147 2415516
1990 Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development. The Journal of cell biology 142 2229189
2003 STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro. Cell and tissue research 113 12883998
2020 TRM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection. Proceedings of the National Academy of Sciences of the United States of America 107 32439709
2003 Direct selection of human bone marrow mesenchymal stem cells using an anti-CD49a antibody reveals their CD45med,low phenotype. British journal of haematology 106 12877680
1988 T lymphocytes compartmentalized on the epithelial surface of the lower respiratory tract express the very late activation antigen complex VLA-1. Clinical immunology and immunopathology 90 3257425
2020 CD49a Regulates Cutaneous Resident Memory CD8+ T Cell Persistence and Response. Cell reports 88 32877667
2007 Collagen distribution and expression of collagen-binding alpha1beta1 (VLA-1) and alpha2beta1 (VLA-2) integrins on CD4 and CD8 T cells during influenza infection. Journal of immunology (Baltimore, Md. : 1950) 71 17372009
2021 Prostate Cancer Peripheral Blood NK Cells Show Enhanced CD9, CD49a, CXCR4, CXCL8, MMP-9 Production and Secrete Monocyte-Recruiting and Polarizing Factors. Frontiers in immunology 67 33569050
2018 Human CD49a+ Lung Natural Killer Cell Cytotoxicity in Response to Influenza A Virus. Frontiers in immunology 67 30079068
2017 ITGA1 is a pre-malignant biomarker that promotes therapy resistance and metastatic potential in pancreatic cancer. Scientific reports 66 28855593
1995 Glomerular epithelial and mesangial cells differentially modulate the binding specificities of VLA-1 and VLA-2. Laboratory investigation; a journal of technical methods and pathology 59 7898055
2017 IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells. Immunity, inflammation and disease 50 28952190
2007 Selection using the alpha-1 integrin (CD49a) enhances the multipotentiality of the mesenchymal stem cell population from heterogeneous bone marrow stromal cells. Journal of molecular histology 48 17694277
1987 Cell matrix adhesion-related proteins VLA-1 and VLA-2: regulation of expression on T cells. Journal of immunology (Baltimore, Md. : 1950) 47 3106495
2023 Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a. Immunity 45 37269830
2021 Hsa_circ_0110757 upregulates ITGA1 to facilitate temozolomide resistance in glioma by suppressing hsa-miR-1298-5p. Cell death & disease 45 33674567
2010 Identification of a unique population of tissue-memory CD4+ T cells in the airways after influenza infection that is dependent on the integrin VLA-1. Journal of immunology (Baltimore, Md. : 1950) 45 20200271
2006 Human and rodent bone marrow mesenchymal stem cells that express primitive stem cell markers can be directly enriched by using the CD49a molecule. Cell and tissue research 45 17109120
2000 Reduced gut intraepithelial lymphocytes in VLA1 null mice. Cellular immunology 45 10805967
1999 Integrin alpha1beta1 (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen. Immunology 45 10457223
1992 Adhesion molecules VLA-1 to VLA-6 define discrete stages of peripheral B lymphocyte development and characterize different types of B cell neoplasia. Leukemia 44 1588789
2003 Expression of the alpha1beta1 integrin, VLA-1, marks a distinct subset of human CD4+ memory T cells. The Journal of clinical investigation 37 14597770
1988 Regulation of proteins in the VLA cell substrate adhesion family: influence of cell growth conditions on VLA-1, VLA-2, and VLA-3 expression. Experimental cell research 37 3292271
1995 Monocyte activation: rapid induction of alpha 1/beta 1 (VLA-1) integrin expression by lipopolysaccharide and interferon-gamma. European journal of immunology 35 7589148
2021 CD49a Identifies Polyfunctional Memory CD8 T Cell Subsets that Persist in the Lungs After Influenza Infection. Frontiers in immunology 32 34566986
1990 Increased expression of laminin/collagen receptor (VLA-1) on epithelium of inflamed human intestine. Journal of clinical pathology 31 2341567
2017 Expression and role of VLA-1 in resident memory CD8 T cell responses to respiratory mucosal viral-vectored immunization against tuberculosis. Scientific reports 30 28842633
1994 Functional regulation of the human integrin VLA-1 (CD49a/CD29) by divalent cations and stimulatory beta 1 antibodies. FEBS letters 30 7516898
2002 Treatment with an antibody to VLA-1 integrin reduces glomerular and tubulointerstitial scarring in a rat model of crescentic glomerulonephritis. The American journal of pathology 29 12368200
1994 Functional role of VLA-1 (CD49A) in adhesion, cation-dependent spreading, and activation of cultured human T lymphocytes. Cellular immunology 29 8025956
1989 A novel monoclonal antibody, 1B3.1, binds to a new epitope of the VLA-1 molecule. Cellular immunology 29 2475259
2011 Combined blockade of VEGFR-3 and VLA-1 markedly promotes high-risk corneal transplant survival. Investigative ophthalmology & visual science 28 21715348
2022 Human-Induced CD49a+ NK Cells Promote Fetal Growth. Frontiers in immunology 27 35185911
2019 CD49a regulates the function of human decidual natural killer cells. American journal of reproductive immunology (New York, N.Y. : 1989) 26 30756436
2017 Derivate Isocorydine (d-ICD) Suppresses Migration and Invasion of Hepatocellular Carcinoma Cell by Downregulating ITGA1 Expression. International journal of molecular sciences 26 28264467
2021 Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8+ T Cells. Cancer immunology research 25 33619119
2022 Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma. Metabolic brain disease 23 36301458
1987 Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis. Annals of the rheumatic diseases 22 2827591
2007 Transcriptional and epigenetic regulation of the integrin collagen receptor locus ITGA1-PELO-ITGA2. Biochimica et biophysica acta 21 17669516
1993 T lymphocytes in giant cell arteritic lesions are polyclonal cells expressing alpha beta type antigen receptors and VLA-1 integrin receptors. Clinical and experimental immunology 20 8383021
2021 Selection for CD26- and CD49A+ Cells From Pluripotent Stem Cells-Derived Islet-Like Clusters Improves Therapeutic Activity in Diabetic Mice. Frontiers in endocrinology 17 34025576
2007 Polymorphisms and haplotypes of integrinalpha1 (ITGA1) are associated with bone mineral density and fracture risk in postmenopausal Koreans. Bone 17 17931993
2024 Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 38169150
2018 Formation and phenotypic characterization of CD49a, CD49b and CD103 expressing CD8 T cell populations in human metastatic melanoma. Oncoimmunology 15 30288359
2020 CD49a+CD49b+ NK cells induced by viral infection reflect an activated state of conventional NK cells. Science China. Life sciences 14 32335843
2023 Antiviral Responses of Tissue-resident CD49a+ Lung Natural Killer Cells Are Dysregulated in Chronic Obstructive Pulmonary Disease. American journal of respiratory and critical care medicine 13 36170617
2018 Cytokine-Based Generation of CD49a+Eomes-/+ Natural Killer Cell Subsets. Frontiers in immunology 13 30319610
2017 The SNP-set based association study identifies ITGA1 as a susceptibility gene of attention-deficit/hyperactivity disorder in Han Chinese. Translational psychiatry 12 28809852
2015 Langerhans Cells Suppress CD49a+ NK Cell-Mediated Skin Inflammation. Journal of immunology (Baltimore, Md. : 1950) 12 26209621
1999 The epidermotropic mycosis fungoides associated alpha1beta1 integrin (VLA-1, CD49a/CD29) is primarily a collagen IV receptor on malignant T cells. Journal of cutaneous pathology 12 10082395
2019 CD49a Expression Identifies a Subset of Intrahepatic Macrophages in Humans. Frontiers in immunology 11 31231382
2014 CD49a promotes T-cell-mediated hepatitis by driving T helper 1 cytokine and interleukin-17 production. Immunology 11 24164540
2013 ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population. World journal of gastroenterology 11 24124332
2008 Synovial VLA-1+ T cells display an oligoclonal and partly distinct repertoire in rheumatoid and psoriatic arthritis. Clinical immunology (Orlando, Fla.) 11 18456562
2002 Interaction of disease-related antigen-reactive T-cell lines from multiple sclerosis patients with type IV collagen: role of integrin VLA-1 and effects of irradiation. Journal of clinical immunology 11 12078857
1992 Genetic mapping of the integrin alpha 1 gene (Vla1) to mouse chromosome 13. Genomics 9 1427867
2018 Taste receptor T1R1/T1R3 promotes the tumoricidal activity of hepatic CD49a+ CD49b- natural killer cells. European journal of immunology 7 30259960
2010 Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction. Thrombosis and haemostasis 7 20076856
2023 Linc00662 m6A promotes the progression and metastasis of pancreatic cancer by activating focal adhesion through the GTF2B-ITGA1-FAK pathway. American journal of cancer research 6 37293163
2019 Synergistic anticancer effect of Grb2 and ITGA1 on cancer cells highly expressing Grb2 through suppressing ERK phosphorylation. International journal of clinical and experimental pathology 6 31933732
2025 Thrombospondin 1 Promotes Cytoskeleton Remodeling, Dedifferentiation, and Pulmonary Metastasis through ITGA1 and ITGA6 in Osteosarcoma. International journal of biological sciences 5 40083708
2022 Distinct Expression Patterns of Genes Coding for Biological Response Modifiers Involved in Inflammatory Responses and Development of Fibrosis in Chronic Hepatitis C: Upregulation of SMAD-6 and MMP-8 and Downregulation of CAV-1, CTGF, CEBPB, PLG, TIMP-3, MMP-1, ITGA-1, ITGA-2 and LOX. Medicina (Kaunas, Lithuania) 5 36556936
2020 Characterization of Rhesus Macaque Liver-Resident CD49a+ NK Cells During Retrovirus Infections. Frontiers in immunology 5 32849583
2020 Novel genetic variants of SYK and ITGA1 related lymphangiogenesis signaling pathway predict non-small cell lung cancer survival. American journal of cancer research 5 32905494
2025 ITGA1, the alpha 1 subunit of integrin receptor, is a novel marker of drug-resistant senescent melanoma cells in vitro. Archives of toxicology 4 40202610
2024 ITGA1 Promotes Glioma Cell Proliferation and Affects Immune Cell Infiltration in Low-Grade Glioma. Mediators of inflammation 4 39502752
2023 High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma. Heliyon 4 38107324
2023 Depleting transforming growth factor beta receptor 2 signalling in the cartilage of itga1-null mice attenuates spontaneous knee osteoarthritis. Osteoarthritis and cartilage open 3 37649532
2022 Melanocyte-specific CD49a+ CD8+ T cells in vitiligo lesion potentiate to maintain activity during systemic steroid therapy. The Journal of dermatology 3 36514908
2021 VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp. Frontiers in immunology 3 33584706
2007 The effect of blockade of tumor necrosis factor alpha on VLA-1+ T-cells in rheumatoid arthritis patients. Journal of clinical immunology 3 17891451
2025 CD49a Targeting Enhances NK Cell Function and Antitumor Immunity. Cancer immunology research 2 39570767
2024 CD4+ T cell help during early acute hepacivirus infection is critical for viral clearance and the generation of a liver-homing CD103+CD49a+ effector CD8+ T cell subset. PLoS pathogens 2 39392861
2025 CD49a+ NK cells promote esophageal cancer development by inducing MDCSs infiltration via GM-CSF. British journal of cancer 1 40437020
2025 Targeting Microglial CD49a Inhibits Neuroinflammation and Demonstrates Therapeutic Potential for Parkinson's Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41462565
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2006 Expression of VLA1, VLA2 and VLA3 Integrin Molecules in Uterine Endometrium of Infertile Women with Unexplained Aetiology in Ahwaz-Iran. Iranian journal of immunology : IJI 1 18685175
2026 Resident CD49a+CD103+NKG2C+ NK cells restrict HIV infection in human lymphoid tissue explants. Science advances 0 41576166
2026 Dual-targeted NIR-II AIE theranostic nanoparticles disrupt HNRNPC-driven ITGA1+ myCAFs differentiation and immune evasion in oral squamous cell carcinoma. Biomaterials 0 41702227
2026 CD133/CD49a discriminate between human pluripotent stem cell-derived pancreatic beta and alpha cells. Stem cell reports 0 41791382
2025 Luteolin Alleviates Diabetic Foot Ulcers Through Improving KDM4C/ITGA1-mediated Functional Impairments of AGEs-Induced Senescent Endothelial Cell. Journal of biochemical and molecular toxicology 0 40778546
2025 Therapeutic targeting of ITGA1 delayed retinoblastoma progression through suppression of STAT3 signaling. Experimental eye research 0 40939856
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