Affinage

IGFBP7

Insulin-like growth factor-binding protein 7 · UniProt Q16270

Length
282 aa
Mass
29.1 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IGFBP7 is a secreted, multivalent signaling modulator that suppresses pro-growth and pro-survival pathways while promoting cellular senescence and apoptosis across diverse tissue contexts. It directly binds the extracellular domain of IGF1R via its N-terminal 97 amino acids, blocking IGF-1/2-induced receptor activation and suppressing downstream PI3K-AKT signaling; it also binds activin A, heparan sulfate proteoglycans (including syndecan-1), and select chemokines (CCL21, CXCL10, CCL5) in the extracellular matrix (PMID:23250396, PMID:10502291, PMID:10859029, PMID:12847218). IGFBP7 transcription is activated by p53 through an intronic response element, by TGF-β1/ALK5/Smad2/4 signaling, and by the SWI/SNF component SMARCB1, and is frequently epigenetically silenced in cancer; its protein stability is regulated by A-to-I RNA editing that alters a matriptase cleavage site (PMID:19638426, PMID:26974954, PMID:23851500, PMID:22750143). As a senescence-associated secretory factor, IGFBP7 drives oncogene-induced senescence downstream of BRAF^V600E by inhibiting BRAF-MEK-ERK signaling and upregulating the proapoptotic protein BNIP3L, and in the heart it promotes cardiomyocyte senescence by suppressing FOXO3a through IGF-1R/IRS/AKT, with endothelial cell-specific deletion or antibody neutralization ameliorating pressure-overload heart failure (PMID:18267069, PMID:39196168, PMID:38991046).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Establishing that IGFBP7 engages the cell surface via heparan sulfate proteoglycans answered how this secreted protein is retained in the pericellular matrix and can exert local effects.

    Evidence Cell adhesion competition, heparinase treatment, and synthetic peptide blocking identified a 20-amino-acid heparan sulfate-binding domain

    PMID:10502291

    Open questions at the time
    • Identity of specific HSPGs mediating the interaction was not resolved beyond later syndecan-1 identification
    • Functional consequence of cell-surface retention on signaling not dissected
  2. 2000 Medium

    Discovery that IGFBP7 binds activin A expanded its ligand repertoire beyond IGFs, suggesting it modulates TGF-β superfamily signaling.

    Evidence Co-immunoprecipitation of IGFBP7 with activin A from conditioned media

    PMID:10859029

    Open questions at the time
    • Single co-IP method without reciprocal validation or competition assay
    • Functional consequence of activin A sequestration on downstream Smad signaling not tested
  3. 2003 Medium

    Multiple studies defined IGFBP7 as a tumor suppressor that operates partly through IGF-independent adhesion to extracellular matrix components and partly through proteolytic regulation of its IGF-binding capacity.

    Evidence Proteolysis assays showed serine protease cleavage abolishes IGF-binding and increases cell attachment via syndecan-1; xenograft and soft-agar assays demonstrated IGF-independent tumor suppression; saturable binding assays identified chemokine partners CCL21, CXCL10, CCL5

    PMID:12847218 PMID:14521955 PMID:17465992

    Open questions at the time
    • In vivo protease identity not established
    • Chemokine-presenting function at HEV not validated beyond binding and calcium-signaling retention
    • Relative contributions of IGF-dependent vs IGF-independent suppression not quantified
  4. 2008 High

    Demonstrating that BRAF^V600E drives IGFBP7 secretion to inhibit MEK-ERK and induce senescence/apoptosis via BNIP3L established IGFBP7 as a critical effector of oncogene-induced senescence.

    Evidence Genome-wide RNAi screen, recombinant protein rescue, and xenograft model in primary cells expressing oncogenic BRAF

    PMID:18267069

    Open questions at the time
    • Whether IGFBP7-mediated OIS generalizes beyond BRAF^V600E to other RAS-pathway oncogenes was not tested
    • Direct receptor mediating BRAF-MEK-ERK suppression not identified in this study
  5. 2008 Medium

    Showing TGF-β1 induces IGFBP7 via ALK5/Smad2 in brain endothelial cells linked IGFBP7 to TGF-β-driven angiogenesis in glioblastoma.

    Evidence TGF-β neutralizing antibody, ALK5 antagonist SB431542, and Smad2 phosphorylation analysis in GBM-conditioned media-treated endothelial cells

    PMID:18711401

    Open questions at the time
    • Pro-angiogenic role in brain endothelium contrasts with anti-angiogenic effects reported elsewhere; context-dependency not resolved
    • Downstream target of IGFBP7 in tube formation not identified
  6. 2009 High

    Identification of a p53 response element in IGFBP7 intron 1 placed IGFBP7 in the p53 tumor-suppressor network and explained its silencing upon p53 loss or promoter methylation.

    Evidence ChIP demonstrating direct p53 binding to intronic element, corroborated by luciferase reporter and 5-aza-dC demethylation rescue

    PMID:19638426

    Open questions at the time
    • Whether p53-dependent induction is the dominant route in vivo vs TGF-β/Smad induction not compared
    • Epigenetic silencing mechanism at the IGFBP7 promoter in cancer not fully dissected
  7. 2012 High

    Mapping the direct IGFBP7–IGF1R interaction to the N-terminal 97 amino acids and showing mutually exclusive binding with IGF-1 established the primary receptor-level mechanism for IGFBP7's anti-growth activity.

    Evidence Co-immunoprecipitation, deletion mutagenesis, receptor internalization, and phosphorylation assays

    PMID:23250396

    Open questions at the time
    • Structural basis of the mutually exclusive binding not determined
    • Whether IGFBP7 also signals through IGF1R independently of simple competitive antagonism not resolved
  8. 2012 Medium

    Discovery that A-to-I RNA editing alters IGFBP7's protease susceptibility introduced a post-transcriptional regulatory layer controlling its functional half-life.

    Evidence RNA editing analysis coupled with proteolysis susceptibility assays; later confirmed with ADAR2 catalytic-dead mutant showing editing prevents matriptase cleavage and stabilizes the protein

    PMID:22750143 PMID:28035363

    Open questions at the time
    • Prevalence of edited vs unedited IGFBP7 transcripts across tissues not systematically surveyed
    • In vivo significance of editing for IGFBP7 tumor suppression not demonstrated
  9. 2013 Medium

    Placing IGFBP7 downstream of the SMARCB1/SWI-SNF chromatin remodeling complex explained IGFBP7 loss in rhabdoid tumors and showed IGFBP7 re-expression alone can substitute for SMARCB1 tumor suppression.

    Evidence SMARCB1 re-expression restored IGFBP7; Igfbp7 re-expression in Smarcb1-deficient cells suppressed xenograft tumor growth

    PMID:23851500

    Open questions at the time
    • Whether SMARCB1 directly binds the IGFBP7 promoter or acts indirectly not resolved
    • Generalizability beyond rhabdoid tumor cells not tested
  10. 2016 Medium

    Confirmation that TGF-β1 induces IGFBP7 through Smad2/4 in renal epithelial cells, and that IGFBP7 is required for TGF-β-driven EMT, extended its role to kidney fibrosis.

    Evidence Smad2/4 knockdown blocked IGFBP7 induction; IGFBP7 knockdown reversed TGF-β1-induced EMT markers

    PMID:26974954

    Open questions at the time
    • Direct binding of Smad2/4 to IGFBP7 regulatory regions not shown
    • Role in progressive renal fibrosis in vivo not established
  11. 2022 High

    In the heart, an Htra3–TGF-β–IGFBP7 axis was delineated in which pressure overload downregulates the protease Htra3 in fibroblasts, unleashing TGF-β to induce cardiomyocyte IGFBP7, which promotes senescence by suppressing FOXO3a via IGF-1R/IRS/AKT signaling.

    Evidence Single-cell RNA-seq, spatial transcriptomics, Igfbp7-KO and AAV9-shRNA knockdown, neutralizing antibody, and pressure-overload mouse models with functional cardiac readouts

    PMID:35672400 PMID:39196168

    Open questions at the time
    • Whether FOXO3a suppression is the sole effector of IGFBP7-driven cardiac senescence not determined
    • Human genetic evidence linking IGFBP7 variants to heart failure absent
  12. 2024 High

    Demonstrating that senescent endothelial cells are the primary cardiac source of IGFBP7 paracrine signaling, and that EC-specific deletion or vaccine-mediated neutralization rescues heart failure, established IGFBP7 as a druggable SASP factor.

    Evidence EC-specific Igfbp7 conditional knockout, anti-IGFBP7 peptide vaccine, single-cell RNA-seq, and metabolic analysis under pressure overload

    PMID:38991046

    Open questions at the time
    • Vaccine efficacy in large-animal or human settings not tested
    • Whether EC- vs cardiomyocyte-derived IGFBP7 has distinct paracrine targets not fully resolved
  13. 2025 High

    Identification of an enteric neuron–ILC3 circuit in which GABA suppresses C/EBPβ-LIP-driven IGFBP7 transcription, with autocrine IGFBP7–IGF1R signaling restraining ILC3 proliferation and IL-17A production, extended the gene's role to intestinal immunity.

    Evidence Conditional neuron ablation, receptor and transcription factor knockdowns, autocrine IGFBP7 assays, and in vivo colitis models

    PMID:40033120

    Open questions at the time
    • Whether IGFBP7 restrains other innate lymphoid populations not tested
    • Relevance to human inflammatory bowel disease not directly demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Unresolved: the structural basis of IGFBP7's mutually exclusive binding to IGF1R versus IGFs, the relative in vivo contributions of its multiple receptor interactions (IGF1R, activin receptors, syndecan-1, HSPGs), and whether its pro-angiogenic vs anti-angiogenic effects reflect distinct receptor complexes in different vascular beds.
  • No crystal structure or cryo-EM structure of IGFBP7–IGF1R complex
  • Context-dependent switching between pro- and anti-angiogenic roles mechanistically unexplained
  • Relative signaling contributions of IGF1R antagonism vs activin A sequestration vs HSPG binding not quantitatively dissected in any single system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0048018 receptor ligand activity 4 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 6 GO:0005886 plasma membrane 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-5357801 Programmed Cell Death 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-168256 Immune System 2
Partners
BNIP3LCCL21CXCL10FOXO3IGF1RINHBASDC1SMAD2

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 BRAFV600E oncogene expression in primary cells leads to synthesis and secretion of IGFBP7, which acts through autocrine/paracrine pathways to inhibit BRAF-MEK-ERK signaling and induce senescence and apoptosis; apoptosis results from IGFBP7-mediated upregulation of BNIP3L, a proapoptotic BCL2 family protein. Genome-wide RNAi screening, recombinant protein treatment, xenograft mouse model, cell-based assays Cell High 18267069
2012 IGFBP7 directly binds to the extracellular portion of IGF1R (via its N-terminal 97 amino acids), blocks its activation and internalization by IGF-1/2, causes accumulation of inactive IGF1R on the cell surface, and suppresses downstream PI3K-AKT signaling; binding of IGFBP7 and IGF-1 to IGF1R is mutually exclusive. Co-immunoprecipitation, deletion mutagenesis, receptor internalization assay, phosphorylation assays, recombinant protein treatment Science signaling High 23250396
2000 IGFBP7 (mac25) protein was co-immunoprecipitated with activin A, indicating that mac25/IGFBP7 is a secreted protein that binds activin A and may modulate its signaling. Immunoprecipitation, Western blot, GFP fusion localization, recombinant protein growth suppression assay Molecular medicine Medium 10859029
1999 IGFBP7 (AGM/mac25) binds to cell-surface heparan sulfates via an identified 20-amino acid cell-binding sequence; heparinase treatment and heparin competition abolish cell adhesion to AGM. Cell adhesion competition assays, heparinase treatment, synthetic peptide blocking, binding assays Journal of cellular biochemistry High 10502291
2003 Proteolytic cleavage of IGFBP7 (IGFBP-rP1) by a trypsin-like serine proteinase abrogates its insulin/IGF-1-binding activity and insulin/IGF-1-dependent growth-stimulatory activity while markedly increasing its cell attachment activity; syndecan-1 is identified as a cell surface receptor for both intact and cleaved forms. Proteolytic processing assays, IGF-1 binding assays, cell attachment assays, receptor identification Biochemical and biophysical research communications Medium 14521955
2003 IGFBP7 (mac25/IGFBP-rP1) overexpression in prostate cancer cells increases SOD-2 (manganese superoxide dismutase) expression as a downstream mediator of its senescence-associated tumor suppression; mac25 cells show increased phospho-ERK and phospho-AKT, and PI3K inhibition markedly decreases their viability. cDNA expression array, stable transfection, in vivo tumor growth, SOD-2 overexpression rescue Oncogene Medium 12592389
2008 TGF-β1 secreted by glioblastoma cells induces IGFBP7 expression in human brain endothelial cells through the TGF-β1/ALK5/Smad-2 signaling pathway; IGFBP7 protein promotes capillary-like tube formation (angiogenesis). Conditioned media treatment, TGF-β neutralizing antibody, ALK5 receptor antagonist (SB431542), Smad-2 phosphorylation assays, Matrigel tube formation assay Oncogene Medium 18711401
2009 IGFBP7 is a p53-responsive gene; p53 induces IGFBP7 expression by binding to a p53 response element within intron 1 of the IGFBP7 gene, as demonstrated by luciferase reporter assay and chromatin immunoprecipitation. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), 5-aza-dC demethylation, p53 transfection Carcinogenesis High 19638426
2016 ADAR2 edits IGFBP7 mRNA (A-to-I RNA editing), and this editing stabilizes IGFBP7 protein by altering the matriptase protease recognition site, preventing proteolytic cleavage; ADAR2-mediated IGFBP7 stabilization induces apoptosis and inhibits Akt signaling in esophageal squamous cell carcinoma. RNA-seq editing analysis, active-site ADAR2 mutant, IGFBP7 knockdown, Western blotting for Akt signaling, in vitro/in vivo tumor models International journal of oncology Medium 28035363
2012 A-to-I RNA editing of IGFBP7 transcripts alters the protein's susceptibility to proteolytic cleavage, providing a mechanism for cells to modulate IGFBP7 functionality through RNA editing. RNA editing analysis, proteolysis susceptibility assays FEBS letters Medium 22750143
2016 TGF-β1 upregulates IGFBP7 expression in human renal proximal tubular epithelial cells via Smad2 and Smad4 (but not MAPK) pathways; knockdown of IGFBP7 reverses TGF-β1-induced epithelial-to-mesenchymal transition (EMT). Dose/time-dependent TGF-β1 treatment, Smad2/4 pathway inhibition, IGFBP7 knockdown, EMT marker analysis PloS one Medium 26974954
2018 IGFBP7 promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells via the Wnt/β-catenin signaling pathway; both overexpression and exogenous IGFBP7 protein increase β-catenin levels, and Wnt/β-catenin inhibitors partially block IGFBP7-induced osteogenesis. Overexpression, exogenous protein addition, siRNA knockdown, Wnt inhibitor treatment, in vivo tibial osteotomy model FASEB journal Medium 29242275
2019 IGFBP7 inhibits RANKL-induced osteoclastogenesis, F-actin ring formation, and bone resorption by suppressing the NF-κB signaling pathway; in a mouse ovariectomy-induced osteoporosis model, IGFBP7 treatment attenuated osteoclast-driven bone loss. Recombinant IGFBP7 protein, lentivirus overexpression, siRNA knockdown, NF-κB pathway analysis, in vivo ovariectomy model Cell proliferation Medium 31889368
2022 Cardiac fibroblasts regulate heart failure via an Htra3-TGF-β-IGFBP7 axis: pressure overload downregulates Htra3, leading to TGF-β activation, which drives cardiomyocyte DNA damage and induction of IGFBP7 secretion from failing cardiomyocytes; Htra3 overexpression inhibits TGF-β signaling and ameliorates cardiac dysfunction. Single-cell RNA-seq, spatial transcriptomics, genetic perturbation (overexpression, knockout), mouse pressure overload model, human plasma proteome analysis Nature communications High 35672400
2022 IGFBP7 promotes cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and ROS detoxification; in vivo AAV9-shRNA cardiac Igfbp7 knockdown and antibody-mediated IGFBP7 neutralization reversed suppression of FOXO3a and attenuated pressure-overload-induced heart failure. Igfbp7 knockout mouse, AAV9-shRNA knockdown, neutralizing antibody treatment, pressure overload model, signaling pathway analysis Nature cardiovascular research High 39196168
2024 Senescent cardiac endothelial cells upregulate Igfbp7 under pressure overload; EC-specific Igfbp7 deletion and vaccine-mediated neutralization of IGFBP7 ameliorated cardiac dysfunction with increased oxidative phosphorylation in cardiomyocytes, establishing IGFBP7 as a paracrine mediator from senescent ECs to cardiomyocytes. EC-specific gene knockout, AAV9 overexpression, anti-IGFBP7 vaccine, single-cell RNA-seq, metabolic analysis Circulation High 38991046
2003 IGFBP7 (mac25/AGM) expressed on cell surfaces reduces anchorage-independent growth and suppresses tumor growth in vivo through an insulin/IGF-independent mechanism; IGFBP7-expressing cells bind more efficiently to fibronectin and laminin-5. RNA interference knockdown, expression vector transfection, soft agar colony assay, xenograft mouse model, cell adhesion assay Cancer science (published 2007) Medium 17465992
2013 SMARCB1 (Snf5) is required for transcriptional activation of IGFBP7; re-introduction of Igfbp7 alone in Smarcb1-deficient tumor cells can hinder tumor development in xenografts, placing IGFBP7 downstream of the SMARCB1/SWI-SNF chromatin remodeling complex. Gene expression profiling, Smarcb1 re-expression, Igfbp7 re-expression, xenograft mouse model Oncogene Medium 23851500
2020 Exercise upregulates Igfbp7 expression in muscle satellite cells, which impedes Akt phosphorylation, inhibits mTOR activity, reduces mitochondrial metabolism, and causes hypoacetylation of H3K27ac at Akt promoters, thereby protecting satellite cells from exhaustion. Treadmill exercise model, RNA sequencing, ChIP-PCR, flow cytometry, immunofluorescence, Akt-mTOR pathway analysis Theranostics Medium 32483463
2003 IGFBP7 (mac25/AGM) interacts with multiple molecules in high endothelial venules including chemokines CCL21 (SLC), CXCL10 (IP-10), and CCL5 (RANTES) in a dose-dependent and saturable manner; binding to chemokines is selective, does not inhibit their Ca2+-signaling activity, and suggests a chemokine-presenting function at the HEV basal lamina. Binding assays (dose-dependent, saturable), competitive inhibition assay, immunohistochemistry, Ca2+-signaling assay Journal of immunology Medium 12847218
2014 IGFBP7 promotes TAM/M2 macrophage polarization in gastric cancer via FGF2/FGFR1/PI3K/AKT axis; exogenous recombinant IGFBP7 treatment of macrophages and cancer cells confirmed this paracrine mechanism. RNA sequencing, ELISA, recombinant IGFBP7 treatment, loss-of-function studies, transcriptome analysis Cell death discovery Medium 36681667
2021 IGFBP7 binds to IGF1R and mediates programmed cell death (necroptosis via RIPK1/RIPK3/MLKL pathway) and inflammation in acute kidney injury; co-immunoprecipitation confirmed IGFBP7 binding to IGF1R, and IGF1R inhibitor (picropodophyllin) abrogated the therapeutic effects of a protective compound targeting this pathway. Co-immunoprecipitation, RNA sequencing, Western blot, in vivo AKI mouse models, IGF1R inhibitor treatment Phytomedicine Medium 33773190
2025 GABA from enteric GABAergic neurons signals through Gabbr1/Gabbr2 receptors on ILC3s to suppress the LIP isoform of C/EBP-β, which in turn represses IGFBP7 transcription; autocrine IGFBP7 then signals through IGF1R to inhibit ILC3 proliferation and IL-17A production. Conditional neuron ablation, receptor knockout, transcription factor knockdown, autocrine IGFBP7 assays, in vivo colitis model Nature immunology High 40033120
2024 IGFBP7 is a key SASP component that induces secondary senescence by: (1) binding insulin and inhibiting its anti-senescence effects; (2) promoting IGF-II interaction with IGF2R while blocking IGF1R; (3) interacting with activin A receptors to induce senescence via SMAD pathways; these effects are dependent on ERK and AKT signaling. Neutralizing antibody treatment, recombinant IGFBP7 incubation, senescence assays, ERK/AKT pathway inhibition, SMAD pathway analysis Cell communication and signaling Medium 39533382
2011 Exogenous IGFBP7 treatment of triple-negative breast cancer cells induces G1 cell cycle arrest, senescence, and apoptosis associated with activation of p38 MAPK, upregulation of p53 and p21(cip1), and cleaved PARP; systemic rIGFBP7 in xenograft mice inhibited tumorigenesis with anti-angiogenic effects. Recombinant protein treatment, flow cytometry cell cycle analysis, SA-β-gal senescence assay, Western blotting, xenograft mouse model Breast cancer research and treatment Medium 21997538
2014 IGFBP7 suppresses VEGFA- and LH-induced angiogenesis in luteal microvascular endothelial cells by inhibiting their proliferation and migration, reducing phosphorylation of MEK and ERK1/2, and attenuating VEGFA-enhanced COX-2 expression and prostaglandin E2 secretion. In vitro tube formation assay (Matrigel), proliferation and migration assays, ERK/MEK phosphorylation assays, COX-2 mRNA and PGE2 measurement The Journal of reproduction and development Medium 25212428
2018 AKI-induced urinary IGFBP7 elevations are not due to stress-induced gene transcription but result from increased glomerular filtration, decreased tubular reabsorption, and proximal tubule cell IGFBP7 leakage; immunohistochemistry showed progressive IGFBP7 loss from injured proximal tubule cells, and endocytic inhibition in normal mice tripled urinary IGFBP7 levels. Mouse AKI models (glycerol, maleate, ischemia), ELISA, mRNA quantification, immunohistochemistry, competitive endocytic inhibition Journal of the American Society of Nephrology Medium 29980651

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 733 18267069
1993 Cloning and characterization of PSF, a novel pre-mRNA splicing factor. Genes & development 334 8449401
2014 Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PloS one 318 24675717
2014 Tissue Inhibitor Metalloproteinase-2 (TIMP-2)⋅IGF-Binding Protein-7 (IGFBP7) Levels Are Associated with Adverse Long-Term Outcomes in Patients with AKI. Journal of the American Society of Nephrology : JASN 186 25535301
2001 PSF is a novel corepressor that mediates its effect through Sin3A and the DNA binding domain of nuclear hormone receptors. Molecular and cellular biology 153 11259580
2007 The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3' processing and transcription termination. Genes & development 151 17639083
2012 IGFBP7 binds to the IGF-1 receptor and blocks its activation by insulin-like growth factors. Science signaling 141 23250396
2022 Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis. Nature communications 122 35672400
1998 Down-regulation of T1A12/mac25, a novel insulin-like growth factor binding protein related gene, is associated with disease progression in breast carcinomas. Oncogene 118 9627112
2010 Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing. Molecular cell 106 20932480
2005 Role for PSF in mediating transcriptional activator-dependent stimulation of pre-mRNA processing in vivo. Molecular and cellular biology 103 16024807
2008 Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-beta signaling. Oncogene 102 18711401
2023 Cancer-associated fibroblast-secreted IGFBP7 promotes gastric cancer by enhancing tumor associated macrophage infiltration via FGF2/FGFR1/PI3K/AKT axis. Cell death discovery 93 36681667
2018 Mechanisms Underlying Increased TIMP2 and IGFBP7 Urinary Excretion in Experimental AKI. Journal of the American Society of Nephrology : JASN 93 29980651
2009 IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype. Carcinogenesis 92 19638426
2015 2'-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF. Nucleic acids research 87 25855809
2020 Insulin Growth Factor Binding Protein 7 (IGFBP7)-Related Cancer and IGFBP3 and IGFBP7 Crosstalk. Frontiers in oncology 84 32500027
2015 Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery? Critical care (London, England) 83 25560277
1998 The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct interaction. The Journal of biological chemistry 79 9756848
2010 Fox-3 and PSF interact to activate neural cell-specific alternative splicing. Nucleic acids research 76 21177649
2000 Messenger ribonucleic acids for MAC25 and connective tissue growth factor (CTGF) are inversely regulated during folliculogenesis and early luteogenesis. Endocrinology 76 10875270
2020 Exercise protects proliferative muscle satellite cells against exhaustion via the Igfbp7-Akt-mTOR axis. Theranostics 73 32483463
2011 IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways. Breast cancer research and treatment 72 21997538
2010 IGFBP7: an oncosuppressor gene in thyroid carcinogenesis. Oncogene 71 20440262
2015 PSF: nuclear busy-body or nuclear facilitator? Wiley interdisciplinary reviews. RNA 69 25832716
2016 ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma. International journal of oncology 68 28035363
2007 Combinatorial control of signal-induced exon repression by hnRNP L and PSF. Molecular and cellular biology 67 17664280
2018 IGFBP7 regulates the osteogenic differentiation of bone marrow-derived mesenchymal stem cells via Wnt/β-catenin signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 64 29242275
2016 Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO. Oncotarget 63 27259250
2000 A secreted tumor-suppressor, mac25, with activin-binding activity. Molecular medicine (Cambridge, Mass.) 60 10859029
2019 Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice. Clinical chemistry and laboratory medicine 58 30179848
2009 Human PSF binds to RAD51 and modulates its homologous-pairing and strand-exchange activities. Nucleic acids research 58 19447914
1996 A follistatin-like gene, mac25, may act as a growth suppressor of osteosarcoma cells. Oncogene 58 8649839
2009 BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest. Cellular signalling 55 19439179
2012 Annexin A2 and PSF proteins interact with p53 IRES and regulate translation of p53 mRNA. RNA biology 54 23131771
2003 Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein-1. Oncogene 53 12592389
2003 A high endothelial venule secretory protein, mac25/angiomodulin, interacts with multiple high endothelial venule-associated molecules including chemokines. Journal of immunology (Baltimore, Md. : 1950) 51 12847218
2019 Analysis of GDF15 and IGFBP7 in Hyperemesis Gravidarum Support Causality. Geburtshilfe und Frauenheilkunde 50 31000883
2017 Urinary TIMP-2 and IGFBP7 for the prediction of acute kidney injury following cardiac surgery. BMC nephrology 50 28558754
2022 MALAT1 modulates alternative splicing by cooperating with the splicing factors PTBP1 and PSF. Science advances 48 36563164
2017 Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery. Pediatric nephrology (Berlin, Germany) 48 28382566
2000 Differential nuclear localization and nuclear matrix association of the splicing factors PSF and PTB. Journal of cellular biochemistry 48 10653975
2022 Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure. Nature cardiovascular research 46 39196168
2012 HIV-1 pre-mRNA commitment to Rev mediated export through PSF and Matrin 3. Virology 46 23158102
2009 hnRNP M interacts with PSF and p54(nrb) and co-localizes within defined nuclear structures. Experimental cell research 46 19874820
2007 Strong suppression of tumor growth by insulin-like growth factor-binding protein-related protein 1/tumor-derived cell adhesion factor/mac25. Cancer science 46 17465992
2015 Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA. RNA (New York, N.Y.) 44 25605962
2017 The diagnostic accuracy of urinary [TIMP-2]·[IGFBP7] for acute kidney injury in adults: A PRISMA-compliant meta-analysis. Medicine 43 28682920
1999 Identification of cell-binding site of angiomodulin (AGM/TAF/Mac25) that interacts with heparan sulfates on cell surface. Journal of cellular biochemistry 41 10502291
2006 Binding of the polypyrimidine tract-binding protein-associated splicing factor (PSF) to the hepatitis delta virus RNA. Virology 40 16938326
2003 Proteolytic processing of IGFBP-related protein-1 (TAF/angiomodulin/mac25) modulates its biological activity. Biochemical and biophysical research communications 40 14521955
2021 Gypenoside XLIX protects against acute kidney injury by suppressing IGFBP7/IGF1R-mediated programmed cell death and inflammation. Phytomedicine : international journal of phytotherapy and phytopharmacology 39 33773190
2020 PSF Promotes ER-Positive Breast Cancer Progression via Posttranscriptional Regulation of ESR1 and SCFD2. Cancer research 39 32213542
2013 Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncology reports 39 23381221
2016 Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells. PloS one 38 26974954
2010 IGFBP7 is a p53 target gene inactivated in human lung cancer by DNA hypermethylation. Lung cancer (Amsterdam, Netherlands) 38 21095038
2000 PSF/p54(nrb) stimulates "jumping" of DNA topoisomerase I between separate DNA helices. Biochemistry 38 10858305
2008 Reactivation of IGFBP7 by DNA demethylation inhibits human colon cancer cell growth in vitro. Cancer biology & therapy 36 18981723
2019 IGFBP7 acts as a negative regulator of RANKL-induced osteoclastogenesis and oestrogen deficiency-induced bone loss. Cell proliferation 35 31889368
2020 Long non-coding RNA ARAP1-AS1 promotes tumorigenesis and metastasis through facilitating proto-oncogene c-Myc translation via dissociating PSF/PTB dimer in cervical cancer. Cancer medicine 33 31953923
2010 Development and characterization of a new epithelial cell line PSF from caudal fin of Green chromide, Etroplus suratensis (Bloch, 1790). In vitro cellular & developmental biology. Animal 33 20577829
2012 Vimentin and PSF act in concert to regulate IbeA+ E. coli K1 induced activation and nuclear translocation of NF-κB in human brain endothelial cells. PloS one 32 22536447
2023 METTL3-mediated m6A modification of IGFBP7-OT promotes osteoarthritis progression by regulating the DNMT1/DNMT3a-IGFBP7 axis. Cell reports 31 37270777
2014 p54nrb/NonO and PSF promote U snRNA nuclear export by accelerating its export complex assembly. Nucleic acids research 31 24413662
2009 Hacking RNA: Hakai promotes tumorigenesis by enhancing the RNA-binding function of PSF. Cell cycle (Georgetown, Tex.) 31 19855157
2024 Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7. Circulation 30 38991046
2018 TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors. Critical care (London, England) 30 29751827
2003 PSF-TFE3 oncoprotein in papillary renal cell carcinoma inactivates TFE3 and p53 through cytoplasmic sequestration. Oncogene 30 12902986
1999 Cortisol enhances the expression of mac25/insulin-like growth factor-binding protein-related protein-1 in cultured osteoblasts. Endocrinology 30 9886829
2014 IGFBP7 induces apoptosis of acute myeloid leukemia cells and synergizes with chemotherapy in suppression of leukemia cell survival. Cell death & disease 29 24967962
2013 Loss of IGFBP7 expression and persistent AKT activation contribute to SMARCB1/Snf5-mediated tumorigenesis. Oncogene 29 23851500
2011 IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase. Leukemia 28 22005787
2022 Optimal precision and accuracy in 4Pi-STORM using dynamic spline PSF models. Nature methods 27 35577958
2019 The effectiveness of urinary TIMP-2 and IGFBP-7 in predicting acute kidney injury in critically ill neonates. Pediatric research 27 31791043
1999 Identification of PSF, the polypyrimidine tract-binding protein-associated splicing factor, as a developmentally regulated neuronal protein. Journal of neuroscience research 27 10397636
2023 PsRGL1 negatively regulates chilling- and gibberellin-induced dormancy release by PsF-box1-mediated targeting for proteolytic degradation in tree peony. Horticulture research 26 37786434
2015 Interaction and colocalization of HERMES/RBPMS with NonO, PSF, and G3BP1 in neuronal cytoplasmic RNP granules in mouse retinal line cells. Genes to cells : devoted to molecular & cellular mechanisms 26 25651939
2010 HSP60, a protein downregulated by IGFBP7 in colorectal carcinoma. Journal of experimental & clinical cancer research : CR 26 20433702
2021 The predictive value of TIMP-2 and IGFBP7 for kidney failure and 30-day mortality after elective cardiac surgery. Scientific reports 25 33441876
2019 Comparison of urinary TIMP-2 and IGFBP7 cut-offs to predict acute kidney injury in critically ill patients: A PRISMA-compliant systematic review and meta-analysis. Medicine 24 31261582
2016 Inhibition of Cervical Cancer by Promoting IGFBP7 Expression Using Ellagic Acid from Pomegranate Peel. Medical science monitor : international medical journal of experimental and clinical research 24 27941714
2015 Relationship between expression of IGFBP7 and clinicopathological variables in gastric cancer. Journal of clinical pathology 24 26043748
2014 PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion. Biochimica et biophysica acta 24 24632473
2012 IGFBP7's susceptibility to proteolysis is altered by A-to-I RNA editing of its transcript. FEBS letters 24 22750143
2002 Characterization of mac25/angiomodulin expression by high endothelial venule cells in lymphoid tissues and its identification as an inducible marker for activated endothelial cells. International immunology 24 12407018
2013 PTB-associated splicing factor (PSF) is a PPARγ-binding protein and growth regulator of colon cancer cells. PloS one 23 23516550
1997 Developmental regulation of Mac25/insulin-like growth factor-binding protein-7 expression in skeletal myogenesis. Experimental cell research 23 9417882
2024 IGFBP7 is a key component of the senescence-associated secretory phenotype (SASP) that induces senescence in healthy cells by modulating the insulin, IGF, and activin A pathways. Cell communication and signaling : CCS 22 39533382
2023 Crosstalk between Cancer Cells and Cancer-Associated Fibroblasts Mediated by TGF-β1-IGFBP7 Signaling Promotes the Progression of Infiltrative Gastric Cancer. Cancers 21 37568781
2018 The Accuracy of Urinary TIMP-2 and IGFBP7 for the Diagnosis of Cardiac Surgery-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis. Journal of intensive care medicine 21 30376758
2015 Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL. BMC cancer 21 26450156
2015 Tissue and serum IGFBP7 protein as biomarker in high-grade soft tissue sarcoma. American journal of cancer research 21 26807324
2014 High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-β and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner. PloS one 21 24427302
2025 Enteric GABAergic neuron-derived γ-aminobutyric acid initiates expression of Igfbp7 to sustain ILC3 homeostasis. Nature immunology 20 40033120
2021 IGFBP7 and GDF-15, but not P1NP, are associated with cardiac alterations and 10-year outcome in an elderly community-based study. BMC cardiovascular disorders 20 34217226
2015 Isolation and Comparative Genomic Analysis of T1-Like Shigella Bacteriophage pSf-2. Current microbiology 20 26612033
2014 Inhibitory effect of insulin-like growth factor-binding protein-7 (IGFBP7) on in vitro angiogenesis of vascular endothelial cells in the rat corpus luteum. The Journal of reproduction and development 20 25212428
2006 Role of PSF-TFE3 oncoprotein in the development of papillary renal cell carcinomas. Oncogene 20 16832349
2019 IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer. Cancers 19 30609749
2012 Proteomic identification of PSF and p54(nrb) as TopBP1-interacting proteins. Journal of cellular biochemistry 19 22213094