Affinage

IGFBP7

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

Length
282 aa
Mass
29.1 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IGFBP7 (mac25/AGM/IGFBP-rP1) is a secreted, matrix-associated glycoprotein that functions as a multi-ligand-binding modulator of growth-factor signaling, principally governing cellular senescence, proliferation arrest, and tissue immune/metabolic homeostasis (PMID:8939990, PMID:18267069, PMID:23250396, PMID:39533382). It binds IGF-I and IGF-II with affinity substantially lower than canonical IGFBPs (PMID:8939990), engages insulin through Arg198/His200 (PMID:27101796), and binds activin A (PMID:10859029), while attaching to cell surfaces and the high-endothelial-venule basal lamina via a defined heparan-sulfate-binding peptide that also serves to present specific chemokines (CCL21, CXCL10, CCL5) and bind VEGF (PMID:10502291, PMID:12847218, PMID:12407018). Its central signaling activity is direct binding to the IGF1R extracellular domain through its N-terminal region, mutually exclusive with IGF-1, which blocks IGF-induced receptor activation, accumulates inactive IGF1R at the surface, and shuts down downstream PI3K-AKT signaling (PMID:23250396); in other contexts IGFBP7 instead prolongs IGF1R surface retention to sustain IGF1R/IRS/AKT/ERK output (PMID:34438446). Through this IGF1R axis IGFBP7 enforces senescence and tumor suppression: it is required for BRAFV600E-induced senescence and apoptosis (via BNIP3L) (PMID:18267069), acts as a p53 target gene through an intron-1 response element (PMID:19638426), drives G1 arrest with elevated p27/p16 and senescence-associated β-galactosidase (PMID:11791184, PMID:31183073), and operates as a key SASP component that propagates secondary senescence by inhibiting insulin, redirecting IGF-II to IGF2R, and engaging activin/SMAD signaling (PMID:39533382). Its tumor-suppressor expression is frequently silenced by CpG-island methylation (PMID:19638426, PMID:20440262). In the heart IGFBP7 promotes cardiac senescence and failure by IGF1R/IRS/AKT-dependent suppression of FOXO3a and impairment of oxidative phosphorylation (PMID:39196168, PMID:38991046), and in vivo loss of Igfbp7 yields constitutive IGF signaling, reduced senescence, and spontaneous tumors (PMID:28619711). IGFBP7 is proteolytically processed on the cell surface by the membrane serine protease matriptase, which abolishes its insulin/IGF-binding and growth-modulating activity while enhancing cell attachment (PMID:14521955, PMID:16420484). Beyond secreted signaling, intracellular IGFBP7 binds PKM2 to promote K433 acetylation, dimerization, and nuclear translocation driving SREBP1-dependent lipogenesis and renal fibrosis (PMID:40346800). It additionally maintains gut immune homeostasis through autocrine ILC3 Igfbp7/Igf1R signaling downstream of GABA/C/EBP-β that restrains IL-17A production (PMID:40033120).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 High

    Established that the orphan protein mac25 is a bona fide IGF-binding protein, defining its molecular identity, while parallel work linked it to growth suppression and the follistatin/TGF-β family.

    Evidence Western ligand blot, affinity cross-linking and competition with recombinant protein; gene transfection clonal-growth assay in osteosarcoma cells

    PMID:8649839 PMID:8939990

    Open questions at the time
    • IGF affinity is far lower than canonical IGFBPs, leaving its physiological IGF-sequestering role unclear
    • tumor-suppressor mechanism only correlatively linked to TGF-β/activin
  2. 1999 High

    Defined how IGFBP7 associates with the extracellular environment and is transcriptionally controlled, establishing it as a matrix/cell-surface protein induced by endocrine signals.

    Evidence Heparan-sulfate-binding peptide mapping with heparinase/GAG competition and tube-formation assay; nuclear run-on assays of cortisol- and PTH-driven transcription in osteoblasts

    PMID:10218947 PMID:10502291 PMID:9886829

    Open questions at the time
    • functional consequence of HS-mediated surface anchoring for downstream signaling not resolved
    • transcriptional control studies confined to osteoblasts
  3. 2000 Medium

    Confirmed IGFBP7 is secreted and directly binds activin A, broadening its ligand repertoire beyond IGFs and connecting it to growth suppression across cell types.

    Evidence Reciprocal co-immunoprecipitation, GFP-fusion localization, and recombinant-protein growth-suppression assays in multiple cell lines

    PMID:10859029

    Open questions at the time
    • functional consequence of activin A binding (sequestration vs presentation) not established
    • single lab
  4. 2002 High

    Tested whether IGFBP7 retains high-affinity IGF/insulin binding and showed it does not by biosensor, recasting it as a low-affinity binder and shifting attention to receptor-level mechanisms; concurrently linked its overexpression to senescence-associated cell-cycle arrest.

    Evidence BIAcore biosensor binding analysis; flow-cytometry cell-cycle analysis, CDK/cyclin immunoblots, kinase assays and SA-β-gal staining in prostate cancer cells

    PMID:11791184 PMID:11956149

    Open questions at the time
    • negative binding result conflicts with ligand-blot data, leaving ligand affinity context-dependent and unresolved
    • senescence mechanism not yet tied to a receptor
  5. 2003 Medium

    Resolved how IGFBP7 is converted between functional states and identified its surface receptors and chemokine-presenting role, establishing proteolysis as a functional switch.

    Evidence Cleavage and binding-activity assays with syndecan-1 identification; saturable chemokine-binding assays with Ca2+-signaling readout and HEV immunohistochemistry; SOD-2 induction by array/Western with xenograft and phospho-ERK/AKT analysis

    PMID:12407018 PMID:12592389 PMID:12847218 PMID:14521955

    Open questions at the time
    • identity of the endogenous protease not yet known
    • relationship between chemokine presentation and growth suppression unaddressed
  6. 2006 High

    Identified matriptase as the physiological enzyme generating the two-chain form, providing the molecular basis for the proteolytic functional switch.

    Evidence Membrane-fraction activity assays, siRNA knockdown of matriptase, and cleavage by purified soluble matriptase at the natural site

    PMID:16420484

    Open questions at the time
    • in vivo physiological contexts where matriptase processing of IGFBP7 dominates not defined
  7. 2008 High

    Placed IGFBP7 in oncogene-induced senescence as a BRAF-pathway effector and a TGF-β/ALK5/Smad2-induced angiogenic factor, defining upstream regulators and a senescence/apoptosis output.

    Evidence Genome-wide RNAi screen, recombinant-protein rescue, BNIP3L analysis and xenografts; TGF-β neutralization/ALK5 inhibition with Smad2 phosphorylation and Matrigel tube formation

    PMID:18267069 PMID:18711401

    Open questions at the time
    • BRAF-IGFBP7 senescence link later contested in melanocytes
    • receptor mediating the senescence signal not yet identified
  8. 2009 High

    Defined p53 as a direct transcriptional activator of IGFBP7 and CpG methylation as the silencing mechanism, integrating it into tumor-suppressor circuitry; also showed anti-angiogenic suppression of VEGF/MEK-ERK.

    Evidence Luciferase reporter, ChIP of p53 at intron-1, 5-aza demethylation rescue; HUVEC tube-formation/proliferation assays with phospho-MEK/ERK and siRNA knockdown

    PMID:19374835 PMID:19638426

    Open questions at the time
    • p53-IGFBP7 axis contribution to senescence in vivo not quantified
  9. 2010 Medium

    Challenged the generality of the BRAF-IGFBP7 senescence model and reinforced methylation-dependent tumor suppression in another lineage, exposing context dependence.

    Evidence Lentiviral IGFBP7 silencing in primary melanocytes/fibroblasts with large-cohort IHC; cDNA and recombinant-protein rescue in hypermethylated thyroid cancer cells

    PMID:20440262 PMID:20478260

    Open questions at the time
    • the contradiction over BRAF-induced senescence remains unreconciled
    • tissue-specific determinants of IGFBP7 dependence undefined
  10. 2012 High

    Identified the central receptor-level mechanism: IGFBP7 binds the IGF1R ectodomain via its N-terminus, mutually exclusive with IGF-1, blocking receptor activation/internalization and PI3K-AKT signaling.

    Evidence IGF1R binding/competition assays, N-terminal deletion mapping, internalization and phospho-AKT/4E-BP1 analyses, apoptosis assays across cell lines

    PMID:23250396

    Open questions at the time
    • does not explain context-dependent sustained signaling later observed
    • structural details of the IGFBP7-IGF1R interface not resolved
  11. 2013 Medium

    Connected IGFBP7 to a chromatin-remodeling tumor-suppressor pathway and identified downstream effectors, deepening its tumor-suppressor mechanism.

    Evidence SMARCB1 re-expression/epistasis with Igfbp7 restoration and xenografts; HSP60 proteomic identification with recombinant-HSP60 rescue; A-to-I RNA editing analysis with edited-IGFBP7 senescence assay

    PMID:20433702 PMID:23543219 PMID:23851500

    Open questions at the time
    • how SMARCB1 activates the IGFBP7 locus mechanistically unclear
    • physiological prevalence of RNA-edited IGFBP7 beyond epidermis unknown
  12. 2014 Medium

    Demonstrated through germline knockout that Igfbp7 supports pro-survival IGF1R/Akt/STAT5 signaling in vivo, revealing a context where it sustains rather than blocks growth signaling.

    Evidence Igfbp7-null mice with mammary involution phenotyping, transcriptomics, and phospho-STAT/Akt/IGF1R analysis

    PMID:24505323

    Open questions at the time
    • mechanism reconciling pro-survival vs anti-IGF1R activities not addressed
    • single tissue context
  13. 2016 Medium

    Mapped the insulin-binding determinants of IGFBP7, providing residue-level basis for its insulin-modulating activity.

    Evidence Molecular dynamics simulation and site-directed double mutagenesis (R198E-H200F) with binding measurement

    PMID:27101796

    Open questions at the time
    • functional consequence of insulin binding for signaling not tested in this study
  14. 2017 High

    Showed in vivo that IGFBP7 loss drives constitutive IGF signaling, reduced senescence, spontaneous tumors and immune evasion, establishing it as a physiological IGF1R-dependent tumor and immune surveillance gene.

    Evidence Igfbp7 knockout mice with carcinogen challenge, IGF1R-inhibitor rescue, dendritic-cell cross-presentation assays, and T-cell-depletion syngeneic tumor models

    PMID:28619711

    Open questions at the time
    • direct molecular basis of immune-surveillance effect not fully dissected
  15. 2018 Medium

    Clarified mechanisms behind IGFBP7 as a clinical AKI biomarker and as a functional ERK1/2-driven mediator of tubular injury, separating its biomarker behavior from its signaling activity.

    Evidence Mouse AKI models with mRNA quantitation and endocytic-inhibition experiments; HK-2 ERK1/2 pathway analysis with PD98059 and CLP in vivo model

    PMID:29980651 PMID:30450602

    Open questions at the time
    • receptor mediating ERK1/2 activation in tubular cells not identified
    • biomarker mechanism (filtration/leakage) distinct from causal injury role
  16. 2019 Medium

    Extended IGFBP7's anti-proliferative AKT/CDK-inhibitor mechanism to thyroid cancer and uncovered an NF-κB-dependent role in restraining osteoclastogenesis and bone loss.

    Evidence Gain/loss-of-function with phospho-AKT and p21/p27 analysis and xenografts; osteoclast differentiation, F-actin and NF-κB analysis with ovariectomy model

    PMID:31183073 PMID:31889368

    Open questions at the time
    • receptor coupling IGFBP7 to NF-κB in osteoclasts undefined
  17. 2020 Medium

    Revealed an epigenetic feedback mechanism whereby IGFBP7 limits Akt/mTOR and mitochondrial metabolism to reduce H3K27ac at Akt promoters, protecting satellite cells from exhaustion.

    Evidence Exercise model with RNA-seq, ChIP-PCR for H3K27ac, Igfbp7 gain/loss-of-function and mTOR pathway analysis

    PMID:32483463

    Open questions at the time
    • link between metabolic suppression and histone acetylation correlative
    • single lab
  18. 2021 High

    Resolved the paradoxical pro-signaling activity: IGFBP7 prolongs IGF1R surface retention to sustain IGF1R/IRS/AKT/ERK signaling and sensitizes the receptor to insulin, supporting leukemia growth.

    Evidence IGFBP7 knockdown and antibody neutralization with surface-retention assays, phospho-signaling immunoblots, insulin-vs-IGF1 equivalence, and in vivo leukemia model; Co-IP confirmation of IGFBP7-IGF1R binding in AKI

    PMID:33773190 PMID:34438446

    Open questions at the time
    • determinants dictating whether IGFBP7 blocks vs sustains IGF1R signaling not defined
    • structural basis of retention versus blockade unknown
  19. 2022 High

    Defined an IGFBP7 cardiac axis: induced via Htra3-TGF-β, it drives IGF1R/IRS/AKT-dependent FOXO3a suppression and senescence, with loss-of-function rescuing heart failure.

    Evidence Igfbp7 KO, AAV9-shRNA cardiac knockdown and neutralizing antibody in pressure-overload models with FOXO3a/AKT/DNA-damage/ROS readouts; single-cell and plasma multi-omics with Htra3 perturbation; trophoblast IGF1R/c-Jun/MMP2/Slug ChIP study

    PMID:35672400 PMID:35900339 PMID:39196168

    Open questions at the time
    • how the same IGF1R axis yields senescence in heart but invasion in trophoblast not reconciled
  20. 2023 Medium

    Showed IGFBP7 shapes the tumor immune microenvironment by driving macrophage M2 polarization through FGF2/FGFR1/PI3K-AKT signaling.

    Evidence RNA-seq, ELISA, recombinant-IGFBP7 macrophage treatment and loss-of-function in cancer-associated fibroblasts

    PMID:36681667

    Open questions at the time
    • receptor on macrophages mediating FGF2 induction not identified
  21. 2024 High

    Consolidated IGFBP7 as a core SASP factor propagating secondary senescence through insulin inhibition, IGF2R/IGF1R redirection and activin/SMAD signaling, and as a senescent-endothelial-derived driver of cardiac metabolic dysfunction.

    Evidence Conditioned-medium transfer, neutralizing antibody, ROS/prostaglandin inhibition and receptor/SMAD analyses; single-cell RNA-seq, AAV9 overexpression, EC-specific knockout, peptide vaccine and metabolic profiling in TAC model

    PMID:38991046 PMID:39533382

    Open questions at the time
    • relative contribution of the three proposed senescence pathways not quantified
  22. 2025 High

    Uncovered intracellular and tissue-homeostatic roles: IGFBP7 binds PKM2 to drive K433 acetylation, nuclear translocation and SREBP1 lipogenesis in renal fibrosis, and operates in an enteric GABA→C/EBP-β→Igfbp7→Igf1R circuit restraining ILC3 IL-17A production.

    Evidence Co-IP, K433 acetylation, dimerization and nuclear-fractionation assays with KO/cKO/KI mice and organoids; conditional Gabbr1 deletion, neuron ablation, Igfbp7 knockdown and ILC3 functional assays

    PMID:40033120 PMID:40346800

    Open questions at the time
    • how a secreted glycoprotein accesses cytosolic PKM2 not mechanistically explained
    • generality of intracellular PKM2 binding beyond renal tubular cells unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The decisive open question is what molecular context determines whether IGFBP7 blocks IGF1R activation versus prolonging its surface retention and sustaining signaling, and how its extracellular receptor functions relate to its intracellular PKM2-binding activity.
  • no structural model of the IGFBP7-IGF1R complex resolving blockade vs retention
  • no reconciliation of conflicting BRAF-senescence reports
  • mechanism by which secreted IGFBP7 reaches cytosolic partners undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 3 GO:0031012 extracellular matrix 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ACTIVIN AIGF1RINSULINMATRIPTASE (ST14)PKM2SYNDECAN-1VEGF

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Recombinant human IGFBP7 (mac25) specifically binds IGF-I and IGF-II, demonstrated by Western ligand blotting after nondenaturing PAGE and affinity cross-linking; binding was competed by unlabeled IGFs but not by a low-affinity IGF-II analog. Affinity for IGF-I and IGF-II is 5–25-fold lower than IGFBP-3. Western ligand blot, affinity cross-linking, competition binding assay with recombinant protein expressed in baculovirus system The Journal of biological chemistry High 8939990
1996 mac25 (IGFBP7) protein exhibits strong structural homology to follistatin and can act as a tumor suppressor by inhibiting clonal growth of p53-deficient osteosarcoma cells when the gene is introduced; this growth suppression may involve modulation of the TGF-β/activin signaling family. Gene transfection into Saos-2 osteosarcoma cells, clonal growth assay Oncogene Medium 8649839
2000 mac25/IGFBP7 protein co-immunoprecipitates with activin A, indicating it is a secreted protein that directly binds activin A; the protein is localized in the cytoplasm and secreted into culture medium, and exogenous recombinant mac25 suppresses growth of HeLa, P19, and Saos-2 cells. Co-immunoprecipitation, Western blot, GFP-fusion localization, recombinant protein growth suppression assay Molecular medicine (Cambridge, Mass.) Medium 10859029
1999 IGFBP7 (AGM/mac25) binds to cell surfaces via interaction of a defined 20-amino-acid sequence with heparan sulfates; heparin, heparan sulfate, and dextran sulfate (but not chondroitin sulfate) inhibited cell adhesion to IGFBP7-coated plates, and heparinase (but not chondroitinase) treatment of cells blocked binding. The identified heparan sulfate-binding peptide also inhibited capillary tube-like structure formation by vascular endothelial cells. Cell adhesion assay, glycosaminoglycan competition, heparinase/chondroitinase treatment, synthetic peptide competition, tube formation assay Journal of cellular biochemistry High 10502291
1999 Cortisol (glucocorticoid) increases mac25/IGFBP-rP1 expression in osteoblasts through transcriptional mechanisms, as shown by nuclear run-on assays; cycloheximide did not alter transcripts, and cortisol did not change mRNA decay rate, indicating direct transcriptional induction. Northern blot, nuclear run-on assay, mRNA decay analysis, cortisol dose-response in osteoblast cultures Endocrinology Medium 9886829
1999 PTH stimulates mac25/IGFBP-rP1 transcription in osteoblasts via a cycloheximide-insensitive, prostaglandin E2-independent pathway; nuclear run-on assay confirmed increased transcription rate; PGE2 also increased expression, but indomethacin did not block PTH's effect. Northern blot, nuclear run-on assay, pharmacological inhibition (indomethacin), osteoblast cultures Endocrinology Medium 10218947
2002 Overexpression of IGFBP-rP1/mac25 in M12 prostate cancer cells causes G1 phase delay, increased p16 and p27, decreased cyclin D1 and p21, increased cyclin E, and aberrant cyclin A expression in sub-G0/G1 apoptotic cells; increased E2F-1/pRb binding and cyclin A/cdk-2 kinase activity were also observed, along with increased senescence-associated beta-galactosidase staining. Cell cycle analysis (flow cytometry), nocodazole synchronization, immunoblot for cyclins/CDK inhibitors, kinase activity assays, pRb immunoprecipitation, SA-β-gal staining Oncogene High 11791184
2002 Binding of IGF-I, IGF-II, and insulin to mac25 (IGFBP7) was below the detection limit of biosensor analysis, in contrast to intact IGFBP-3 which binds IGFs with high affinity. This is a negative finding that contradicts some earlier reports of IGF binding. Biosensor (BIAcore) binding analysis with recombinant proteins Endocrinology Medium 11956149
2003 Increased expression of IGFBP-rP1/mac25 in LNCaP prostate cancer cells upregulates manganese superoxide dismutase (SOD-2), identified by cDNA expression array and confirmed by Western blot; SOD-2 upregulation mediates part of the senescence-associated tumor suppression effect of mac25. PI3K inhibition markedly decreased viability of mac25-expressing M12 cells, and phosphorylated Erk and Akt were increased in mac25-transfected M12 and LNCaP cells. cDNA expression array, Western blot, xenograft tumor growth assay, PI3K inhibition, phospho-Erk/Akt immunoblot Oncogene Medium 12592389
2003 mac25/IGFBP7 (angiomodulin/AGM) expressed in high endothelial venules binds dose-dependently and saturably to specific chemokines SLC (CCL21), IP-10 (CXCL10), and RANTES (CCL5), but not to 18 other chemokines; binding of mac25/AGM did not abolish Ca2+-signaling activity of SLC and IP-10, suggesting a chemokine-presenting function in HEV basal lamina. Direct binding assay (dose-response, saturation), competition binding, Ca2+ signaling assay, immunohistochemistry co-localization Journal of immunology (Baltimore, Md. : 1950) Medium 12847218
2003 Proteolytic cleavage of IGFBP-rP1 to a two-chain form by a trypsin-like serine proteinase abolishes insulin/IGF-1 binding activity and insulin/IGF-1-dependent growth-stimulatory activity, while markedly increasing cell attachment activity; syndecan-1 was identified as a cell surface receptor for both intact and cleaved forms. Biochemical cleavage analysis, binding activity assay, cell adhesion assay, heparin-binding assay, syndecan-1 receptor identification Biochemical and biophysical research communications Medium 14521955
2006 The membrane-bound serine proteinase matriptase (MT-SP1) is identified as the endogenous processing enzyme that cleaves IGFBP-rP1 to its two-chain form on the cell surface; siRNA knockdown of matriptase in OVISE cells blocked IGFBP-rP1 cleavage, and purified soluble matriptase cleaved IGFBP-rP1 at the same site as natural cleavage. Membrane fraction activity assay, immunoblotting, siRNA knockdown, purified matriptase cleavage assay The FEBS journal High 16420484
2008 BRAFV600E expression in primary cells induces synthesis and secretion of IGFBP7, which acts through autocrine/paracrine pathways to inhibit BRAF-MEK-ERK signaling and induce senescence and apoptosis; apoptosis involves IGFBP7-mediated upregulation of BNIP3L. Genome-wide RNAi screening identified IGFBP7 as required for BRAFV600E-mediated proliferation block. Systemically administered recombinant IGFBP7 suppresses BRAFV600E-positive tumor growth in xenografts. Genome-wide RNAi screen, recombinant protein treatment, xenograft tumor assay, signaling pathway analysis (MEK-ERK), BNIP3L expression analysis Cell High 18267069
2008 IGFBP7 expression in brain endothelial cells is induced by TGF-β1 secreted by GBM tumor cells via the TGF-β1/ALK5/Smad-2 pathway; both TGF-β neutralizing antibody and ALK5 antagonist SB431542 blocked IGFBP7 induction and Smad-2 phosphorylation. IGFBP7 promotes capillary-like tube formation in Matrigel. Conditioned medium treatment, ELISA, neutralizing antibody, pharmacological inhibition (SB431542), Matrigel tube formation assay, Smad-2 phosphorylation analysis Oncogene Medium 18711401
2009 IGFBP7 is a p53-responsive gene; luciferase reporter assay and chromatin immunoprecipitation demonstrated that p53 binds a response element within intron 1 of IGFBP7 and induces its expression. Epigenetic silencing by DNA methylation (associated with low H3K4 methylation) blocks p53-induced IGFBP7 expression in colorectal cancer cells. Luciferase reporter assay, chromatin immunoprecipitation (ChIP), 5-aza-2'-deoxycytidine demethylation, histone modification analysis Carcinogenesis High 19638426
2009 IGFBP7 suppresses VEGF-induced tube formation, proliferation, and phosphorylation of MEK and ERK1/2 in HUVECs; it also attenuates VEGF-enhanced COX-2 and VEGF mRNA expression and PGE2 secretion. Knockdown of endogenous IGFBP7 enhanced COX-2 and VEGF mRNA expression. IGFBP7 did not induce apoptosis in the presence of VEGF. HUVEC tube formation assay, proliferation assay, phospho-MEK/ERK Western blot, qRT-PCR, siRNA knockdown, PGE2 ELISA European journal of pharmacology Medium 19374835
2010 B-RAF signaling does not induce IGFBP7 expression in human melanocytes or fibroblasts, and IGFBP7 is dispensable for B-RAFV600E-induced senescence; lentiviral silencing of IGFBP7 did not prevent BRAF-induced senescence. No correlation between B-RAF mutational status and IGFBP7 protein expression was found in 22 melanoma cell lines, 90 melanomas, and 46 nevi. This contradicts the earlier Wajapeyee et al. (2008) report. Lentiviral shRNA silencing, immunohistochemistry (22 cell lines, 90 melanomas, 46 nevi), IGFBP7 mRNA/protein analysis Cell Medium 20478260
2010 IGFBP7 overexpression in thyroid cancer NIM1 cells (which silence IGFBP7 by promoter hypermethylation) reduced growth rate, migration, and anchorage-independent growth, and induced apoptosis; these effects were observed both with exogenous recombinant IGFBP7 and cDNA transfection. cDNA transfection, recombinant protein treatment, growth assay, migration assay, soft agar colony assay, apoptosis assay Oncogene Medium 20440262
2012 IGFBP7 binds to the extracellular portion of IGF1R, with binding mutually exclusive with IGF-1; the N-terminal 97 amino acids of IGFBP7 are important for IGF1R binding. IGFBP7 pretreatment blocks IGF-1/2-induced IGF1R activation and internalization, accumulates inactive IGF1R on the cell surface, and blocks downstream PI3K-AKT signaling. Prolonged IGFBP7 exposure activates 4E-BP1 and enhances apoptosis in IGF1R-positive cells. IGF1R binding assay, competition with IGF-1, N-terminal deletion mutants, IGF1R internalization assay, phospho-AKT Western blot, 4E-BP1 activation assay, apoptosis assay Science signaling High 23250396
2013 SMARCB1/Snf5 is required for transcriptional activation of IGFBP7; re-introduction of Smarcb1 in Smarcb1-deficient tumor cells restores Igfbp7 expression. Re-introduction of Igfbp7 alone inhibited tumor development in xenografts, placing IGFBP7 downstream of SMARCB1 in a tumor suppression pathway. Gene re-expression, gene expression profiling, xenograft tumor assay, epistasis analysis Oncogene Medium 23851500
2003 mac25/AGM is localized exclusively to the basal lamina of high endothelial venules (HEV) in mouse lymph nodes (not luminal or lateral regions) and is induced in activated endothelial cells by pro-inflammatory cytokines such as TNF-α in vitro; mac25/AGM also binds VEGF and localizes to the subendothelium. Immunohistochemistry with precise compartment analysis, TNF-α stimulation in vitro, co-localization with VEGF International immunology Medium 12407018
2006 A novel protein 25.1 interacts with mac25/IGFBP-rP1; collective overexpression of both proteins in NSCLC cells induced neuroendocrine-like differentiation within 6 hours. mac25/IGFBP-rP1 expression is upregulated concomitantly with cAMP-induced NE differentiation in NCI-H157 cells. Protein interaction (prior study), lentiviral overexpression, morphological differentiation assay, gene expression analysis Oncogene Low 16302002
2016 Computational modeling combined with mutagenesis identified His200 and Arg198 in IGFBP7 as key residues for insulin binding; single mutations R198E or H200F did not significantly weaken binding, but double mutation R198E-H200F markedly reduced insulin binding affinity. Molecular dynamics simulation, site-directed mutagenesis, binding affinity measurement Scientific reports Medium 27101796
2017 Igfbp7-deficient mice show constitutively active IGF signaling, increased hepatocyte proliferation, decreased senescence, spontaneous liver and lung tumors, and proinflammatory/immunosuppressive microenvironments; these proliferative effects were blocked by IGF1R inhibitor treatment. Igfbp7 loss also impairs antigen cross-presentation by dendritic cells and reduces immune surveillance genes in liver. IGFBP7 overexpression inhibited HCC growth in immunocompetent mice in a CD4+/CD8+ T-cell-dependent manner. Igfbp7 knockout mice, carcinogen treatment, IGF1R inhibitor rescue, dendritic cell cross-presentation assay, T-cell depletion in syngeneic model, MEF proliferation/senescence assays Cancer research High 28619711
2018 AKI-induced increases in urinary TIMP-2 and IGFBP7 are not due to stress-induced gene transcription (mRNAs remain at normal levels after AKI induction); instead, increased filtration, decreased tubular reabsorption, and proximal tubule cell leakage are the mechanisms. Competitive inhibition of endocytic protein reabsorption in normal mice tripled urinary IGFBP7 levels. Mouse AKI models, mRNA quantitation, ELISA, immunohistochemistry, endocytic inhibition experiment Journal of the American Society of Nephrology : JASN Medium 29980651
2019 IGFBP7 inhibits RANKL-induced osteoclastogenesis, F-actin ring formation, and bone resorption in vitro via inhibition of the NF-κB signaling pathway; in a mouse ovariectomy model, IGFBP7 treatment attenuated osteoporotic bone loss by inhibiting osteoclast activity. Recombinant IGFBP7 protein treatment, lentiviral overexpression, siRNA knockdown, osteoclast differentiation assay, F-actin staining, NF-κB pathway analysis, ovariectomy mouse model Cell proliferation Medium 31889368
2019 IGFBP7 inhibits cell proliferation in thyroid carcinoma by suppressing phosphorylation-mediated AKT activation and kinase activity, leading to upregulation of CDK inhibitors p27Kip1 and p21Cip1 and G1/S cell cycle arrest; IGFBP7 silencing had opposite effects. IGFBP7 overexpression and siRNA silencing, phospho-AKT Western blot, CDK inhibitor analysis, cell cycle flow cytometry, xenograft tumor assay Cell & bioscience Medium 31183073
2020 Exercise upregulates Igfbp7 in muscle satellite cells, which impedes Akt phosphorylation, inhibits mTOR activity, and limits mitochondrial metabolism; the resulting suppression of mitochondrial metabolism causes hypoacetylation of H3K27 at Akt promoters, reducing Akt transcription and protecting satellite cells from exhaustion. ChIP-PCR confirmed reduced H3K27ac enrichment at Akt promoters. Treadmill exercise model, RNA sequencing, flow cytometry, immunofluorescence, ChIP-PCR for H3K27ac, Igfbp7 gain/loss-of-function, mTOR pathway analysis Theranostics Medium 32483463
2021 IGFBP7 prolongs surface retention of IGF1R under insulin/IGF1 stimulation, resulting in sustained IGF1R, IRS-1, AKT, and ERK phosphorylation; IGFBP7 knockdown or antibody neutralization attenuated ALL cell viability in vitro and leukemia progression in vivo. In the presence of IGFBP7, 25 ng/mL insulin activates IGF1R to levels equivalent to 5 ng/mL IGF1. The insulin receptor was not affected by IGFBP7. IGFBP7 knockdown, antibody neutralization, IGF1R surface retention assay, phospho-signaling Western blot, in vivo leukemia model Blood advances High 34438446
2022 IGFBP7 promotes cardiac senescence by stimulating IGF-1R/IRS/AKT-dependent suppression of FOXO3a, preventing DNA repair and ROS detoxification; AAV9-shRNA cardiac myocyte Igfbp7 knockdown attenuated cardiac dysfunction in pressure-overload model. Antibody-mediated IGFBP7 neutralization reversed FOXO3a suppression, restored DNA repair and ROS detoxification signals, and attenuated heart failure. Igfbp7 KO mouse, AAV9-shRNA cardiac knockdown, IGFBP7 neutralizing antibody in vivo, FOXO3a/AKT/IRS signaling analysis, DNA damage assays, ROS assays, pressure-overload model Nature cardiovascular research High 39196168
2022 Cardiac IGFBP7 is induced downstream of the Htra3-TGF-β pathway; pressure overload downregulates Htra3 in cardiac fibroblasts, activating TGF-β signaling, which induces IGFBP7 secretion from failing cardiomyocytes. IGFBP7 is identified as the most predictable marker of advanced heart failure based on integrative analyses of single-cardiomyocyte transcriptome and plasma proteome. Single-cell RNA-seq, spatial transcriptomics, genetic perturbation, Htra3 overexpression (pressure overload model), plasma proteomics Nature communications Medium 35672400
2024 Senescent cardiac endothelial cells upregulate Igfbp7 expression; Igfbp7 overexpression in murine heart using AAV9 exacerbated cardiac dysfunction, while EC-specific deletion ameliorated it. Vaccine targeting Igfbp7 ameliorated cardiac dysfunction with increased oxidative phosphorylation in cardiomyocytes under pressure overload. IGFBP7 downregulates insulin signaling and oxidative phosphorylation in cardiomyocytes. Single-cell RNA-seq, AAV9 overexpression, EC-specific gene knockout, peptide vaccine, transverse aortic constriction model, metabolic analysis (CE-TOF-MS) Circulation High 38991046
2021 Gypenoside XLIX reduces IGFBP7 levels and its binding to IGF1R in AKI; co-immunoprecipitation showed IGFBP7 binds IGF1R, and IGF1R inhibitor (picropodophyllin) abrogated therapeutic effects of the compound on cisplatin-induced renal injury, confirming IGFBP7/IGF1R-mediated programmed cell death as a pathway in AKI. Co-immunoprecipitation, Western blot, RNA sequencing, pharmacological IGF1R inhibition, cisplatin and IRI mouse AKI models Phytomedicine : international journal of phytotherapy and phytopharmacology Medium 33773190
2018 IGFBP7 regulates sepsis-induced AKI through ERK1/2 signaling; LPS increased IGFBP7 expression and activated ERK1/2 in HK-2 cells; IGFBP7 overexpression induced G1-G0 cell cycle arrest and apoptosis via ERK1/2 (with altered Cyclin D1, p21, Bax, Bcl-2), and these effects were inhibited by the ERK1/2 inhibitor PD98059. IGFBP7 knockdown alleviated CLP-induced renal injury in vivo. siRNA knockdown, overexpression vector, ERK1/2 inhibitor PD98059, cell cycle analysis, apoptosis assay, CLP mouse model Journal of cellular biochemistry Medium 30450602
2013 IGFBP7 overexpression in RKO colorectal cancer cells downregulates HSP60, identified by 2D gel electrophoresis and mass spectrometry and confirmed by Western blot and ELISA; recombinant HSP60 restored proliferation and colony formation in IGFBP7-expressing cells, placing HSP60 as a downstream mediator of IGFBP7 tumor suppression. 2D-PAGE, mass spectrometry, Western blot, ELISA, recombinant protein rescue experiment Journal of experimental & clinical cancer research : CR Medium 20433702
2014 Loss of Igfbp7 in mice causes precocious mammary gland involution during lactation; Igfbp7-null lactating glands show increased and activated STAT3, decreased STAT5, increased Igfbp5, decreased IGF-1 receptor expression, and decreased Akt activation, indicating that Igfbp7 supports cell survival signaling to prevent premature involution. Igfbp7-null mouse generation, mammary gland morphology, transcriptome profiling, phospho-STAT3/STAT5 immunoblot, IGF-1R/Akt analysis PloS one Medium 24505323
2013 A-to-I RNA editing within the IGFBP7 coding sequence occurs at two sites in normal human epidermis; this editing is significantly reduced in basal cell carcinoma and squamous cell carcinoma. The edited form of IGFBP7 inhibits proliferation and induces senescence in HaCaT keratinocytes, identifying RNA editing as a post-transcriptional regulatory mechanism for IGFBP7 function in skin. Sequencing of BCC/SCC/normal epidermis samples, edited IGFBP7 overexpression in HaCaT cells, proliferation assay, senescence assay Archives of dermatological research Medium 23543219
2024 IGFBP7 is a key SASP component that induces secondary senescence; ROS-prostaglandin signaling mediates IGFBP7 release. IGFBP7 induces senescence through three pathways: (1) binding to insulin to inhibit its anti-senescence effects, (2) promoting IGF-II interaction with IGF2R while blocking IGF1R, and (3) interacting with activin A receptors and inducing senescence via SMAD pathways. Neutralizing antibodies against IGFBP7 attenuated SASP pro-senescence activity. Conditioned medium transfer, IGFBP7 neutralizing antibody, ROS/prostaglandin inhibition, receptor binding analysis, SMAD pathway analysis, ERK/AKT signaling assays Cell communication and signaling : CCS Medium 39533382
2025 IGFBP7 in renal tubular epithelial cells binds PKM2 (pyruvate kinase M2), promoting acetylation of PKM2 at K433, which enhances PKM2 dimerization and nuclear translocation, subsequently accelerating lipid production and renal fibrosis via SREBP1-dependent mechanisms. IGFBP7 KO or TEC-conditional KO attenuated renal fibrosis; IGFBP7 knock-in enhanced it. Drug screening identified salmeterol as an IGFBP7 antagonist. Co-immunoprecipitation (IGFBP7-PKM2), K433 acetylation analysis, PKM2 dimerization assay, nuclear fractionation, IGFBP7-KO and conditional KO mice, knock-in mice, kidney organoids, SREBP1 pathway analysis, drug screening Molecular therapy : the journal of the American Society of Gene Therapy High 40346800
2025 Enteric GABAergic neuron-derived GABA signals through ILC3 receptors Gabbr1/Gabbr2 to suppress expression of the LIP isoform of C/EBP-β in ILC3s, which de-represses transcription of Igfbp7; autocrine Igfbp7 signaling through Igf1R inhibits ILC3 proliferation and IL-17A production, thereby maintaining gut immune homeostasis. Conditional deletion of Gabbr1, GABAergic neuron ablation, Igfbp7 knockdown/neutralization, C/EBP-β isoform analysis, ILC3 proliferation and IL-17A assays, transcriptional analysis of Igfbp7 promoter Nature immunology High 40033120
2023 Cancer-associated fibroblast-secreted IGFBP7 promotes macrophage M2 polarization via upregulation and secretion of FGF2, which signals through FGFR1/PI3K/AKT axis; exogenous recombinant IGFBP7 treatment of macrophages confirmed this pathway. FGFR1 is upregulated in M2 but downregulated in M1 polarization. RNA sequencing, qRT-PCR, ELISA, recombinant IGFBP7 treatment of macrophages, loss-of-function studies, transcriptome analysis of macrophage polarization Cell death discovery Medium 36681667
2022 IGFBP7 promotes trophoblast invasion via the IGF-1R-mediated c-Jun signaling pathway; IGFBP7 inactivates IGF-1R, which increases c-Jun binding to MMP2 and Slug promoters, upregulating their transcription and promoting invasion. IGFBP7 depletion in URSA inhibits MMP2 and Slug expression and trophoblast invasion; CsA upregulates IGFBP7 expression. IGFBP7 overexpression and knockdown in HTR-8/SVneo cells, IGF-1R inhibition, ChIP assay (c-Jun binding to MMP2/Slug promoters), invasion assay, Western blot Reproduction (Cambridge, England) Medium 35900339

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 737 18267069
1996 Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. The Journal of biological chemistry 341 8939990
1995 Enhanced expression of an insulin growth factor-like binding protein (mac25) in senescent human mammary epithelial cells and induced expression with retinoic acid. Proceedings of the National Academy of Sciences of the United States of America 189 7538673
2012 IGFBP7 binds to the IGF-1 receptor and blocks its activation by insulin-like growth factors. Science signaling 143 23250396
2022 Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis. Nature communications 128 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
2008 Glioblastoma-secreted factors induce IGFBP7 and angiogenesis by modulating Smad-2-dependent TGF-beta signaling. Oncogene 103 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 100 36681667
2018 Mechanisms Underlying Increased TIMP2 and IGFBP7 Urinary Excretion in Experimental AKI. Journal of the American Society of Nephrology : JASN 94 29980651
2009 IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype. Carcinogenesis 92 19638426
2020 Insulin Growth Factor Binding Protein 7 (IGFBP7)-Related Cancer and IGFBP3 and IGFBP7 Crosstalk. Frontiers in oncology 85 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) 84 25560277
2009 Insulin-like growth factor binding protein-7 (IGFBP7) blocks vascular endothelial cell growth factor (VEGF)-induced angiogenesis in human vascular endothelial cells. European journal of pharmacology 76 19374835
2000 Messenger ribonucleic acids for MAC25 and connective tissue growth factor (CTGF) are inversely regulated during folliculogenesis and early luteogenesis. Endocrinology 76 10875270
2011 IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways. Breast cancer research and treatment 75 21997538
2020 Exercise protects proliferative muscle satellite cells against exhaustion via the Igfbp7-Akt-mTOR axis. Theranostics 74 32483463
2010 IGFBP7: an oncosuppressor gene in thyroid carcinogenesis. Oncogene 72 20440262
2006 Insulin resistance is associated with increased serum concentration of IGF-binding protein-related protein 1 (IGFBP-rP1/MAC25). Diabetes 66 16873698
2000 Methylation and downregulated expression of mac25/insulin-like growth factor binding protein-7 is associated with liver tumorigenesis in SV40T/t antigen transgenic mice, screened by restriction landmark genomic scanning for methylation (RLGS-M). Biochemical and biophysical research communications 66 10623583
2018 IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure. Circulation. Heart failure 64 30354399
2002 Over-expression of insulin-like growth factor binding protein-related protein-1(IGFBP-rP1/mac25) in the M12 prostate cancer cell line alters tumor growth by a delay in G1 and cyclin A associated apoptosis. Oncogene 64 11791184
2017 IGFBP7 Deletion Promotes Hepatocellular Carcinoma. Cancer research 60 28619711
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 59 30179848
1996 A follistatin-like gene, mac25, may act as a growth suppressor of osteosarcoma cells. Oncogene 58 8649839
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
2022 Insulin-like growth factor-binding protein-7 (IGFBP7) links senescence to heart failure. Nature cardiovascular research 52 39196168
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) 52 12847218
2019 Analysis of GDF15 and IGFBP7 in Hyperemesis Gravidarum Support Causality. Geburtshilfe und Frauenheilkunde 50 31000883
2010 IGFBP7 is not required for B-RAF-induced melanocyte senescence. Cell 50 20478260
2022 Insulin-like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence. ESC heart failure 47 36088651
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
2002 Binding properties of insulin-like growth factor binding protein-3 (IGFBP-3), IGFBP-3 N- and C-terminal fragments, and structurally related proteins mac25 and connective tissue growth factor measured using a biosensor. Endocrinology 44 11956149
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 42 33773190
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
2013 Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncology reports 40 23381221
2003 Proteolytic processing of IGFBP-related protein-1 (TAF/angiomodulin/mac25) modulates its biological activity. Biochemical and biophysical research communications 40 14521955
2010 IGFBP7 is a p53 target gene inactivated in human lung cancer by DNA hypermethylation. Lung cancer (Amsterdam, Netherlands) 38 21095038
2019 IGFBP7 acts as a negative regulator of RANKL-induced osteoclastogenesis and oestrogen deficiency-induced bone loss. Cell proliferation 37 31889368
2008 Reactivation of IGFBP7 by DNA demethylation inhibits human colon cancer cell growth in vitro. Cancer biology & therapy 37 18981723
2006 Identification of membrane-bound serine proteinase matriptase as processing enzyme of insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1/angiomodulin/mac25). The FEBS journal 36 16420484
2024 Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7. Circulation 32 38991046
2023 METTL3-mediated m6A modification of IGFBP7-OT promotes osteoarthritis progression by regulating the DNMT1/DNMT3a-IGFBP7 axis. Cell reports 32 37270777
2018 TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors. Critical care (London, England) 32 29751827
2006 Neuroendocrine-like differentiation of non-small cell lung carcinoma cells: regulation by cAMP and the interaction of mac25/IGFBP-rP1 and 25.1. Oncogene 32 16302002
2019 IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma. Cell & bioscience 30 31183073
1999 Cortisol enhances the expression of mac25/insulin-like growth factor-binding protein-related protein-1 in cultured osteoblasts. Endocrinology 30 9886829
2013 Loss of IGFBP7 expression and persistent AKT activation contribute to SMARCB1/Snf5-mediated tumorigenesis. Oncogene 29 23851500
2008 Circulating IGF-binding protein 7 (IGFBP7) levels are elevated in patients with endometriosis or undergoing diabetic hemodialysis. Reproductive biology and endocrinology : RB&E 29 19019211
2021 The predictive value of TIMP-2 and IGFBP7 for kidney failure and 30-day mortality after elective cardiac surgery. Scientific reports 28 33441876
2022 IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction: Findings From DAPA-HF. JACC. Heart failure 27 36592046
2019 The effectiveness of urinary TIMP-2 and IGFBP-7 in predicting acute kidney injury in critically ill neonates. Pediatric research 27 31791043
2010 HSP60, a protein downregulated by IGFBP7 in colorectal carcinoma. Journal of experimental & clinical cancer research : CR 26 20433702
2025 Enteric GABAergic neuron-derived γ-aminobutyric acid initiates expression of Igfbp7 to sustain ILC3 homeostasis. Nature immunology 25 40033120
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 25 39533382
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
2015 Relationship between expression of IGFBP7 and clinicopathological variables in gastric cancer. Journal of clinical pathology 24 26043748
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
1997 Developmental regulation of Mac25/insulin-like growth factor-binding protein-7 expression in skeletal myogenesis. Experimental cell research 23 9417882
2023 TIMP-2 and IGFBP7 in human kidney biopsies in renal disease. Clinical kidney journal 22 37664566
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 22 30376758
2003 Generation of anti-insulin-like growth factor-binding protein-related protein 1 (IGFBP-rP1/MAC25) monoclonal antibodies and immunoassay: quantification of IGFBP-rP1 in human serum and distribution in human fluids and tissues. The Journal of clinical endocrinology and metabolism 22 12843194
2024 Insulin-like growth factor-binding protein 7 (IGFBP7): A microenvironment-dependent regulator of angiogenesis and vascular remodeling. Frontiers in cell and developmental biology 21 39045455
2021 Tissue inhibitor metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) best predicts the development of acute kidney injury. Heliyon 21 34541359
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
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
2019 IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer. Cancers 20 30609749
2020 Urinary [TIMP-2] × [IGFBP7] and serum procalcitonin to predict and assess the risk for short-term outcomes in septic and non-septic critically ill patients. Annals of intensive care 19 32318859
2019 Downregulated IGFBP7 facilitates liver metastasis by modulating epithelial‑mesenchymal transition in colon cancer. Oncology reports 19 31545454
2021 Physiologic IGFBP7 levels prolong IGF1R activation in acute lymphoblastic leukemia. Blood advances 18 34438446
2020 IGFBP7 aggravates sepsis-induced acute lung injury by activating the ERK1/2 pathway. Folia histochemica et cytobiologica 18 33326113
2019 Insulin-like growth factor-binding protein 7 (IGFBP 7) as a new biomarker in coronary heart disease. Advances in medical sciences 18 30769262
2015 Low levels of IGFBP7 expression in high-grade serous ovarian carcinoma is associated with patient outcome. BMC cancer 18 25886299
2012 Analysis of APC and IGFBP7 promoter gene methylation in Swedish and Vietnamese colorectal cancer patients. Oncology letters 18 23255887
2022 Urinary NGAL, IGFBP-7, and TIMP-2: novel biomarkers to predict contrast medium-induced acute kidney injury in children. Renal failure 17 36120960
2019 IGFBP7 regulates sepsis-induced epithelial-mesenchymal transition through ERK1/2 signaling. Acta biochimica et biophysica Sinica 17 31287495
2010 Expression of IGFBP7 in acute leukemia is regulated by DNA methylation. Cancer science 17 21040219
2023 Angiogenesis modulated by CD93 and its natural ligands IGFBP7 and MMRN2: a new target to facilitate solid tumor therapy by vasculature normalization. Cancer cell international 16 37660019
2023 Depletion of Igfbp7 alleviates zebrafish NAFLD progression through inhibiting hepatic ferroptosis. Life sciences 16 37714372
2022 IGFBP7 enhances trophoblast invasion via IGF-1R/c-Jun signaling in unexplained recurrent spontaneous abortion. Reproduction (Cambridge, England) 16 35900339
2021 IGFBP7-AS1 is a p53-responsive long noncoding RNA downregulated by Epstein-Barr virus that contributes to viral tumorigenesis. Cancer letters 16 34634383
2018 Epigenetic Downregulation and Growth Inhibition of IGFBP7 in Gastric Cancer. Asian Pacific journal of cancer prevention : APJCP 16 29580038
1999 Parathyroid hormone increases mac25/insulin-like growth factor-binding protein-related protein-1 expression in cultured osteoblasts. Endocrinology 16 10218947
2018 Silence of IGFBP7 suppresses apoptosis and epithelial mesenchymal transformation of high glucose induced-podocytes. Experimental and therapeutic medicine 15 30112052
2016 Interaction between IGFBP7 and insulin: a theoretical and experimental study. Scientific reports 14 27101796
2000 Decreased expression of mac25 mRNA in uterine leiomyomata compared with adjacent myometrium. American journal of reproductive immunology (New York, N.Y. : 1989) 14 10698042
2021 SNORD116 and growth hormone therapy impact IGFBP7 in Prader-Willi syndrome. Genetics in medicine : official journal of the American College of Medical Genetics 13 34040195
2021 IGFBP7 overexpression promotes acquired resistance to AZD9291 in non-small cell lung cancer. Biochemical and biophysical research communications 13 34303194
2020 Oxidative stress, neutrophil elastase and IGFBP7 levels in patients with oropharyngeal cancer and chronic periodontitis. Oral diseases 13 32333474
2018 IGFBP7 regulates sepsis-induced acute kidney injury through ERK1/2 signaling. Journal of cellular biochemistry 13 30450602
2014 Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland. PloS one 13 24505323
2011 Function and expression of insulin-like growth factor-binding protein 7 (IGFBP7) gene in childhood acute myeloid leukemia. Pediatric hematology and oncology 13 21413833
2025 Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis. Molecular therapy : the journal of the American Society of Gene Therapy 12 40346800
2022 Urinary TIMP-2 and IGFBP-7 protein levels as early predictors of acute kidney injury after cardiac surgery. Journal of cardiac surgery 12 35001430
2019 IGFBP7 contributes to epithelial-mesenchymal transition of HPAEpiC cells in response to radiation. Journal of cellular biochemistry 12 30834595
2019 Urinary [TIMP-2] × [IGFBP-7] for predicting acute kidney injury in patients undergoing orthotopic liver transplantation. BMC nephrology 12 31315590
2019 IGFBP7 downregulation or overexpression effect on bovine preadipocyte differentiation. Animal biotechnology 12 31339434
2015 IGFBP7 functions as a potential lymphangiogenesis inducer in non-small cell lung carcinoma. Oncology reports 12 26706909
2013 Insulin-like growth factor-binding protein-7 (IGFBP7) transcript: A-to-I editing events in normal and cancerous human keratinocytes. Archives of dermatological research 12 23543219

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