Affinage

AEBP1

Adipocyte enhancer-binding protein 1 · UniProt Q8IUX7

Length
1158 aa
Mass
130.9 kDa
Annotated
2026-06-09
68 papers in source corpus 29 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AEBP1 encodes two functionally distinct isoforms — an intracellular transcriptional regulator (AEBP1) and a secreted extracellular matrix protein (ACLP) — that together govern collagen matrix assembly, fibroblast activation, and signaling-dependent proliferation across many tissues (PMID:29606302, PMID:24344132). As a secreted protein, ACLP binds fibrillar collagens directly through its discoidin domain and promotes collagen polymerization; bi-allelic loss-of-function AEBP1 variants produce defective collagen fibril assembly in patient skin, establishing a Mendelian connective-tissue disorder (PMID:29606302). ACLP drives fibroblast-to-myofibroblast differentiation, inducing SMA via TGFβ-receptor-dependent Smad3 phosphorylation and collagen via a TGFβ-receptor-independent route (PMID:24344132), a fibrogenic program recurrently deployed in cancer-associated fibroblasts, where cancer-cell-derived TGFβ1 induces ACLP to sustain CAF activation and matrix contraction (PMID:37686580, PMID:35732215). In its intracellular role, AEBP1 acts as a transcriptional regulator with a C-terminal DNA-binding region, functioning largely as a corepressor whose carboxypeptidase domain is required for repressor activity (PMID:16538615); it occupies promoters genome-wide and directly binds defined target promoters to either activate (BMP4, DDR2, PI3KCβ) or repress (PRKCA, LIPA) transcription (PMID:22723309, PMID:38237535, PMID:41083137, PMID:31601918, PMID:39670965, PMID:41880326). AEBP1 amplifies multiple proliferative and inflammatory signaling axes: it physically interacts with IκBα to accelerate its degradation and potentiate canonical NF-κB signaling in macrophages and vascular smooth muscle (PMID:20396415, PMID:31462616), represses PPARγ/LXRα to impair macrophage cholesterol efflux and promote atherosclerosis (PMID:20419060, PMID:21687917), and feeds into PI3K/AKT signaling — binding the p110β subunit directly to impair insulin signaling in skeletal muscle (PMID:40618921) and acting upstream of AKT in glioma (PMID:33391492). In vivo genetic models establish that AEBP1 controls stromal-epithelial crosstalk in the mammary gland, Wnt/β-catenin-dependent osteoblast differentiation and bone mass, and astrocyte cholesterol catabolism via cytoplasmic sequestration of NPAS3 and consequent LIPA repression in amyloid pathology (PMID:22114697, PMID:41231548, PMID:41880326). At the tumor-stroma interface, autocrine AEBP1 binds CKAP4 on the CAF surface to drive AKT/PD-L1 signaling and suppress T cell cytotoxicity (PMID:40890191).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 Medium

    Established AEBP1 as an in vivo regulator of survival signaling, showing it lowers PTEN levels through direct interaction to promote adipocyte hyperplasia and obesity.

    Evidence AEBP1-overexpressing transgenic mice with protein-interaction and PTEN immunoblot

    PMID:16307171

    Open questions at the time
    • Interaction surface and mechanism of PTEN destabilization not mapped
    • Sex-specific phenotype not explained mechanistically
  2. 2006 Medium

    Defined the molecular basis of AEBP1's intracellular transcriptional repressor activity, mapping a C-terminal basic DNA-binding/calmodulin-binding region and showing the carboxypeptidase domain is required for repression.

    Evidence Luciferase reporter and EMSA with deletion/point mutagenesis in CHO cells

    PMID:16538615

    Open questions at the time
    • Weak direct DNA binding implies a corepressor mode not fully defined
    • Catalytic role of carboxypeptidase domain in repression unresolved
    • Single lab, single study
  3. 2010 Medium

    Linked AEBP1 to inflammatory and lipid-handling transcriptional programs in macrophages, showing it potentiates NF-κB by promoting IκBα turnover and represses PPARγ/LXRα-driven cholesterol efflux.

    Evidence IκBα physical interaction, NF-κB and nuclear-receptor reporter assays, macrophage cholesterol efflux assays

    PMID:20396415 PMID:20419060

    Open questions at the time
    • Mechanism of IκBα degradation (E3 recruitment vs. direct) not defined
    • How a transcriptional repressor mechanistically downregulates PPARγ/LXRα activity unclear
  4. 2011 High

    Provided in vivo proof that macrophage AEBP1 is pro-atherogenic and that stromal AEBP1 controls mammary secretory activation, establishing cell-non-autonomous AEBP1 functions.

    Evidence Transgenic and knockout mice with bone marrow transplantation into ApoE/LDLR models and mammary rescue

    PMID:21687917 PMID:22114697

    Open questions at the time
    • Direct molecular targets in vivo not pinpointed
    • Relative contribution of NF-κB vs PPARγ/LXRα arms in atherosclerosis not separated
  5. 2012 High

    Connected stromal AEBP1 to epithelial transformation and mapped genome-wide AEBP1 promoter occupancy, defining a GAAAT consensus motif and proliferation/apoptosis target set.

    Evidence Bone marrow transplantation with TNFα neutralization and co-culture; ChIP-chip with ChIP-PCR and reporter validation in glioma cells

    PMID:22723309 PMID:22995915

    Open questions at the time
    • Direct vs corepressor binding at GAAAT sites not resolved
    • Co-factors mediating activation vs repression at targets unknown
  6. 2013 High

    Mechanistically separated ACLP-induced myofibroblast outputs and placed AEBP1 in a drug-resistance signaling circuit, showing SMA induction is TGFβ-receptor/Smad3-dependent while collagen induction is receptor-independent.

    Evidence Recombinant ACLP treatment with TGFβ receptor inhibitor and phospho-Smad3 readout; PI3K/Akt-CREB-AEBP1-NF-κB pathway dissection in PLX4032-resistant melanoma

    PMID:24201813 PMID:24344132

    Open questions at the time
    • Receptor/signaling intermediate for TGFβ-independent collagen induction unidentified
    • How ACLP engages the TGFβ receptor not defined
  7. 2019 High

    Defined AEBP1 as a direct transcriptional activator of PI3KCβ and a determinant of death-pathway choice in glioma, and established its pro-inflammatory role in aneurysm.

    Evidence ChIP/promoter binding (AE-1 element) with PIK3CB overexpression rescue in PTEN-isogenic glioma cells; rat elastase AAA model with adenoviral silencing

    PMID:31462616 PMID:31601918

    Open questions at the time
    • How PTEN status switches caspase-dependent vs parthanatos death not fully resolved
    • Direct vs corepressor binding at the AE-1 element unclear
  8. 2022 Medium

    Established ACLP as a self-reinforcing driver of CAF activation, identifying an ACLP-PPARγ-ACLP feedback loop and MMP1/MMP3 induction in pancreatic cancer stroma.

    Evidence Gain/loss-of-function in CAFs with PPARγ modulation, invasion and in vivo metastasis assays

    PMID:35732215

    Open questions at the time
    • Mechanism by which ACLP suppresses PPARγ not defined
    • Direct ACLP receptor on CAFs not identified
  9. 2023 Medium

    Generalized ACLP/AEBP1 as a TGFβ-inducible driver of stromal fibrosis and immune exclusion across tissues, from OSCC CAFs to diabetic retinal pericytes and renal tubular Wnt/β-catenin signaling.

    Evidence TGFβ1 co-culture, collagen contraction and T cell migration assays; scRNA-seq with pericyte siRNA; UUO model with constitutively active β-catenin rescue

    PMID:36738398 PMID:37686580 PMID:37917183

    Open questions at the time
    • Mechanism connecting AEBP1 to β-catenin stabilization not defined
    • Whether intracellular AEBP1 or secreted ACLP drives each phenotype not always disambiguated
  10. 2024 Medium

    Extended the direct-promoter-binding repertoire of AEBP1, showing transcriptional activation of BMP4 in thyroid cancer and repression of PRKCA in cerebral ischemia, and identified AEBP1 as a negative regulator of myogenesis.

    Evidence CRISPR KO with ChIP/reporter and BMP4 rescue; ChIP/reporter with PRKCA inhibitor rescue in MCAO model; gain/loss-of-function in human myoblasts

    PMID:38237535 PMID:39521917 PMID:39670965

    Open questions at the time
    • What dictates AEBP1 activation vs repression at different promoters unknown
    • Co-regulators at BMP4/PRKCA promoters not identified
  11. 2025 High

    Resolved direct AEBP1 protein interactions driving signaling — binding p110β to impair insulin signaling, binding CKAP4 to drive AKT/PD-L1-mediated T cell suppression — and established Wnt/β-catenin-dependent control of bone mass.

    Evidence Docking/co-IP/SPR for p110β with skeletal-muscle insulin assays; fibroblast-specific KO with AEBP1-CKAP4 interaction and Chem-0199 disruption; OsxCre conditional KO with BIO rescue

    PMID:40618921 PMID:40890191 PMID:41231548

    Open questions at the time
    • Structural interface of AEBP1-CKAP4 and AEBP1-p110β not solved
    • How extracellular/autocrine AEBP1 signals through a surface receptor mechanistically unresolved
  12. 2026 High

    Defined AEBP1's mechanism in astrocyte cholesterol catabolism and amyloid pathology — cytoplasmic sequestration of NPAS3 to repress LIPA — and placed AEBP1 downstream of TWIST1 in fibroblast-driven arthritis.

    Evidence Astrocyte-specific manipulation in 5xFAD mice with NPAS3 fractionation and LIPA rescue; CIA model with TWIST1 inhibition and AEBP1 modulation

    PMID:41787682 PMID:41880326

    Open questions at the time
    • Whether intracellular AEBP1 sequesters NPAS3 directly or via partners unclear
    • Generalizability of NPAS3-LIPA axis beyond astrocytes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single gene's two isoforms — a corepressor/activator transcription factor and a secreted collagen-binding ECM protein — coordinate to produce convergent fibrotic and proliferative phenotypes, and what cell-surface receptor transduces extracellular AEBP1/ACLP signaling, remain unresolved.
  • No structural model distinguishing isoform-specific functions
  • Cell-surface receptor for secreted ACLP beyond CKAP4 not defined
  • Logic governing transcriptional activation vs repression at direct targets unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005576 extracellular region 3 GO:0005634 nucleus 3 GO:0031012 extracellular matrix 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CKAP4NFKBIANPAS3PIK3CBPTEN

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 ACLP (AEBP1 extracellular isoform) enhances collagen polymerization and binds directly to several fibrillar collagens via its discoidin domain, as demonstrated by in vitro collagen polymerization assays and binding experiments; loss-of-function bi-allelic AEBP1 variants cause defective collagen fibril assembly in patient skin biopsies. In vitro collagen polymerization assay, direct binding assays, electron microscopy of patient skin biopsies, exome sequencing with functional validation American journal of human genetics High 29606302
2006 AEBP1 functions as a transcriptional repressor of the aP2 gene; its DNA-binding domain was mapped to a C-terminal basic region by EMSA, but wild-type AEBP1 does not interact strongly with DNA, suggesting it acts predominantly as a corepressor. The carboxypeptidase domain is critical for transcriptional repressor activity. AEBP1 also interacts with Ca2+/calmodulin through the same basic C-terminal region. Luciferase reporter assay in CHO cells, electrophoretic mobility shift assay (EMSA), deletion/point mutagenesis, homology modeling Proteins Medium 16538615
2010 AEBP1 physically interacts with IκBα and promotes NF-κB transcriptional activity in macrophages; AEBP1-mediated downregulation of IκBα leads to enhanced NF-κB activation, establishing AEBP1 as a positive regulator of the canonical NF-κB pathway in macrophages. Protein-protein interaction (physical interaction with IκBα demonstrated), NF-κB reporter assays, macrophage gain/loss-of-function experiments Mediators of inflammation Medium 20396415
2010 AEBP1 negatively regulates PPARγ1 and LXRα transcriptional activity in macrophages, thereby impeding cholesterol efflux mediators (ABCA1, ABCG1, ApoE) and promoting foam cell formation. Reporter assays, macrophage cholesterol efflux assays, gain/loss-of-function in macrophages Nuclear receptor signaling Medium 20419060
2005 AEBP1 negatively regulates PTEN through a direct protein-protein interaction; transgenic overexpression of AEBP1 leads to reduced PTEN levels and hyperactivation of survival signaling in adipose tissue, promoting adipocyte hyperplasia and diet-induced obesity in female mice. Transgenic mouse model (AEBP1 overexpression), protein-protein interaction, western blot for PTEN levels, histological analysis of adipose tissue Molecular medicine (Cambridge, Mass.) Medium 16307171
2013 Recombinant ACLP induces myofibroblast differentiation (SMA and collagen expression) in lung fibroblasts. ACLP-induced SMA expression occurs via TGFβ receptor-dependent Smad3 phosphorylation and nuclear translocation, while ACLP-induced collagen expression is TGFβ receptor-independent. ACLP knockdown slows fibroblast-to-myofibroblast transition. Recombinant protein treatment, siRNA knockdown, phospho-Smad3 immunoblot, nuclear translocation assay, TGFβ receptor kinase inhibitor, bleomycin fibrosis mouse model The Journal of biological chemistry High 24344132
2013 AEBP1 is upregulated in PLX4032-resistant melanoma cells due to hyperactivation of PI3K/Akt-CREB signaling, and AEBP1 in turn activates NF-κB by accelerating IκBα degradation, establishing a PI3K/Akt-CREB-AEBP1-NF-κB pathway that confers resistance to BRAF inhibition. PI3K/Akt pathway inhibition, AEBP1 overexpression/knockdown, IκBα degradation assay, NF-κB reporter assay, patient tumor samples Cell death & disease Medium 24201813
2011 Macrophage-specific AEBP1 overexpression promotes atherosclerosis via reduced expression of PPARγ1, LXRα, ABCA1, and ABCG1 and increased inflammatory mediators IL-6 and TNFα. Ablation of AEBP1 significantly attenuates atherosclerosis. Bone marrow transplantation experiments confirmed that the pro-atherogenic effects are macrophage-mediated. Transgenic mouse model, AEBP1 knockout mice, bone marrow transplantation into ApoE-/- and LDLR-/- mice, quantitative lesion analysis, gene expression Molecular medicine (Cambridge, Mass.) High 21687917
2012 Stromal macrophage AEBP1 overexpression induces mammary epithelial hyperplasia via NF-κB/TNFα-mediated paracrine signaling and induction of sonic hedgehog (Shh) in macrophages, leading to Gli1 and Bmi1 expression in mammary epithelium. Bone marrow transplantation of AEBP1-transgenic cells into non-transgenic mice recapitulates alveolar hyperplasia. Transgenic mouse model, bone marrow transplantation, co-culture experiments, conditioned media, TNFα neutralizing antibody, reporter assays for NF-κB The Journal of biological chemistry High 22995915
2012 AEBP1 occupies genomic promoter sites in glioma cells (U87MG) and regulates a large set of genes involved in proliferation and apoptosis. A consensus binding motif GAAAT was identified in 66% of ChIP-chip-identified target promoters and validated by luciferase reporter assay. AEBP1 silencing reduces glioma cell proliferation and survival and promotes apoptosis. ChIP-chip with Agilent human promoter tiling array, ChIP-PCR validation, siRNA knockdown, luciferase reporter assay, qRT-PCR Molecular cancer research : MCR Medium 22723309
2011 AEBP1-null female mice display failed mammary gland secretory activation at parturition, with cytoplasmic lipid droplet accumulation in mammary epithelial cells and milk protein accumulation, resulting in 100% neonatal lethality. Transplanting wild-type bone marrow (stromal AEBP1 restoration) rescues the mammary gland defect, indicating AEBP1 controls stromal-epithelial crosstalk. AEBP1 knockout mouse model, bone marrow transplantation rescue, histological analysis, immunostaining PloS one High 22114697
2019 AEBP1 down-regulation in PTEN-deficient glioma cells (U87MG, U138MG) triggers PARP-1 hyperactivation (parthanatos-like cell death) rather than caspase-dependent apoptosis, with AIF mitochondrial release and nuclear translocation. In PTEN-proficient cells, AEBP1 knockdown induces caspase-dependent apoptosis. AEBP1 positively regulates PI3KCβ by binding the AE-1 element in its promoter, and loss of PI3KCβ causes excessive DNA damage. siRNA knockdown, PARP-1 activation assay, AIF translocation imaging, caspase activity assay, ChIP/promoter binding assay, PIK3CB overexpression rescue, PTEN-reconstitution experiment Scientific reports High 31601918
2019 AEBP1 promotes AAA development by activating the NF-κB pathway in vascular smooth muscle cells, leading to upregulation of pro-inflammatory factors and matrix metalloproteinases (MMPs). In vivo AEBP1 knockdown via intra-adventitial adenovirus suppresses AAA progression in a rat elastase model. Rat AAA model (elastase), in vivo adenoviral AEBP1 silencing, siRNA/overexpression in human vascular smooth muscle cells, NF-κB inhibitor BAY 11-7082, western blot, ELISA Journal of atherosclerosis and thrombosis Medium 31462616
2021 ACT001 (parthenolide derivative) blocks TGF-β-activated AEBP1/AKT signaling in glioma stem-like cells. AEBP1 knockdown impairs AKT phosphorylation and GSC proliferation, and constitutively active AKT rescues AEBP1 depletion-inhibited proliferation, placing AEBP1 upstream of PI3K/AKT in GSCs. siRNA knockdown, constitutively active AKT rescue, PI3K inhibitor, ACT001 treatment, orthotopic xenograft model, RNA-Seq Theranostics Medium 33391492
2023 AEBP1 siRNA knockdown in human retinal pericytes (high glucose conditions) reduces expression of profibrotic markers, and AEBP1 is upregulated in myofibroblast clusters of proliferative diabetic retinopathy fibrovascular membranes, establishing a role for AEBP1 in pericyte-to-myofibroblast transdifferentiation. Single-cell RNA-seq (scRNA-seq) of patient membranes, siRNA knockdown in human retinal pericytes under high-glucose conditions, fibrotic marker immunostaining JCI insight Medium 37917183
2023 ACLP in cancer-associated fibroblasts (CAFs) of oral squamous cell carcinoma is induced by cancer-cell-derived TGF-β1; ACLP contributes to CAF activation (collagen gel contraction), promotes cancer cell migration and invasion, and attenuates CD8+ T cell migration into tumors. Co-culture with OSCC cells and TGF-β1 treatment, collagen gel contraction assay, Boyden chamber migration assay, in vivo tumor formation, immunohistochemistry Cancers Medium 37686580
2022 In pancreatic cancer CAFs, ACLP promotes CAF activation and cancer cell invasion via upregulation of MMP1 and MMP3. An ACLP-PPARγ-ACLP positive feedback loop was identified in PDAC CAFs, where ACLP suppresses PPARγ (which normally represses ACLP), sustaining CAF activation. siRNA/overexpression in CAFs, CAF activation marker assays, MMP1/MMP3 expression analysis, PPARγ modulation, invasion assays, in vivo metastasis model Cancer letters Medium 35732215
2023 AEBP1 knockdown in renal tubular cells and in vivo (UUO model) inhibits renal fibrosis by blocking nuclear β-catenin and its downstream targets (Axin2, Myc, Ccnd1). Constitutively active β-catenin-S33Y restores fibrotic gene expression after AEBP1 silencing, placing AEBP1 upstream of the Wnt/β-catenin pathway in renal fibrosis. siRNA knockdown, UUO mouse model, constitutively active β-catenin rescue, western blot, collagen staining, EMT marker analysis Human cell Medium 36738398
2024 AEBP1 promotes papillary thyroid cancer progression by directly binding the BMP4 promoter and driving its transcription (established by dual-luciferase reporter and ChIP assay). BMP4 overexpression rescues the growth/invasion inhibition caused by AEBP1 knockout, placing AEBP1 upstream of BMP4 in PTC. AEBP1 CRISPR knockout, RNA-sequencing, dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), BMP4 overexpression rescue, xenograft mouse model Neoplasia (New York, N.Y.) High 38237535
2024 AEBP1 transcriptionally represses PRKCA expression (established by luciferase reporter and ChIP). Loss of PI3K/AKT signaling due to reduced PRKCA after AEBP1 silencing leads to neuron ferroptosis and impaired microglia M2 polarization in cerebral ischemia/reperfusion; PRKCA inhibition reverses the protective effects of AEBP1 knockdown. siRNA knockdown, luciferase reporter assay, ChIP, PRKCA/PI3K-AKT inhibitor rescue, OGD/R cell model, MCAO mouse model, ROS/GSH/iron assays Drug development research Medium 39670965
2025 Autocrine AEBP1 in cancer-associated fibroblasts binds CKAP4 on the CAF surface, activating AKT/PD-L1 signaling to suppress T cell cytotoxicity. Fibroblast-specific AEBP1 deletion enhances T cell cytotoxicity and suppresses tumor growth. A small molecule (Chem-0199) identified by molecular docking disrupts the AEBP1-CKAP4 interaction and synergizes with anti-PD-1. RNA-seq, scRNA-seq, fibroblast-specific AEBP1 knockout mice, molecular docking, direct protein-protein interaction assay (AEBP1-CKAP4), AKT/PD-L1 signaling assays, syngeneic tumor models Nature communications High 40890191
2025 AEBP1 directly binds the DDR2 promoter to drive its transcription, promoting LPS-induced ferroptosis and inflammatory/M1 microglial polarization via STAT3/P53 signaling in BV2 cells. DDR2 knockdown counteracted the pathological effects of AEBP1. Luciferase reporter assay, ChIP assay (AEBP1 binding to DDR2 promoter), siRNA knockdown, STAT3/P53 pathway inhibition, ferroptosis markers, microglial polarization assays Archives of biochemistry and biophysics Medium 41083137
2025 AEBP1 directly interacts with PI3K (p110β subunit) as demonstrated by protein docking, co-immunoprecipitation, and surface plasmon resonance (SPR). AEBP1 overexpression impairs insulin signaling and glucose transport in skeletal muscle cells, exacerbating insulin resistance; AEBP1 knockdown reverses these changes. Protein docking, co-immunoprecipitation (co-IP), surface plasmon resonance (SPR), AEBP1 overexpression/knockdown in C2C12 and human skeletal muscle cells, insulin signaling assays Metabolism: clinical and experimental High 40618921
2026 ACLP (AEBP1 extracellular isoform) regulates pro-fibrotic transcription factors and genes including MRTFB, RUNX2, SM22, and COL1A1 in cardiac fibroblasts. Fibroblast-specific and cardiac-specific Aebp1 knockout in mice improves cardiac function in ischemia and pressure-overload models. In ex vivo human myocardial tissue, ACLP overexpression in non-failing hearts induces pathological remodeling, while AEBP1 knockdown in failing hearts induces structural reverse remodeling. Fibroblast-specific knockout mice (myocardial ischemia and pressure-overload models), cardiac-specific knockdown, ex vivo human myocardial tissue culture (ACLP overexpression/AEBP1 KD), RNA sequencing for downstream targets Research squarepreprint Medium 42245802
2026 In astrocytes, AEBP1 sequesters NPAS3 in the cytoplasm, reducing NPAS3 binding to the LIPA promoter and thereby repressing LIPA (lysosomal acid lipase) expression. AEBP1-mediated LIPA repression leads to lipid droplet accumulation, excess cholesteryl ester storage, and lysosomal Aβ retention. Astrocyte-specific AEBP1 knockdown ameliorates, while overexpression worsens, amyloid-β pathology in 5×FAD mice. Astrocyte-specific AEBP1 knockdown and overexpression in 5×FAD mice, NPAS3 nuclear/cytoplasmic fractionation, LIPA promoter binding (chromatin analysis), LIPA overexpression rescue, hippocampal transcriptomics and metabolomics Cell reports High 41880326
2025 Aebp1 loss in osteoprogenitors (OsxCre conditional KO) reduces bone mass and impairs osteoblast differentiation. Mechanistically, Aebp1 deletion attenuates Wnt/β-catenin signaling in bone. Restoration of Wnt/β-catenin by injecting BIO (GSK3 inhibitor) substantially rescues bone mass reduction in Aebp1-KO mice. OsxCre conditional knockout mice, siRNA knockdown in primary osteoblasts, Wnt/β-catenin signaling assays, BIO (GSK3 inhibitor) rescue, bone histomorphometry JCI insight High 41231548
2026 TWIST1 directly regulates AEBP1 transcription in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis; AEBP1 in turn activates TGFβ signaling to drive fibroblast activation, migration, and proliferation, and induces POSTN expression to promote angiogenesis. Intra-articular AEBP1 modulation and pharmacological TWIST1 inhibition by harmine alters synovial hyperplasia and bone erosion in CIA mice. Bulk RNA-seq, proteomics, scRNA-seq, functional assays for FLS activation/migration/proliferation, CIA mouse model with AEBP1 intra-articular modulation, harmine (TWIST1 inhibitor) treatment Arthritis & rheumatology (Hoboken, N.J.) Medium 41787682
2025 AEBP1 knockout in CAFs (both isoforms) decreases CAF proliferation, collagen gel contractility, and CAF-mediated tumor cell proliferation. AEBP1 KO downregulates collagen biosynthesis and ECM organization pathways in both mouse and human CAFs, reduces tumor EMT signature in vivo, and enhances anti-PD-1 efficacy. CRISPR gene editing (combined KO of both isoforms), collagen gel contractility assay, co-implantation mouse model, RNA-seq, anti-PD-1 combination treatment in syngeneic models Molecular cancer therapeutics Medium 41024581
2025 AEBP1 mediates TWIST1-driven endothelial proliferation and COL4A1 upregulation; in atherosclerotic plaques, TWIST1 induces AEBP1 transcription which upregulates COL4A1 to drive endothelial cell proliferation and plaque collagen deposition. Single-cell RNA-seq of murine atherosclerotic plaques with inducible Twist1 ECKO, transcriptional analysis of AEBP1-COL4A1 axis bioRxivpreprint Low
2024 AEBP1 is a negative regulator of skeletal muscle differentiation; AEBP1 knockdown in human skeletal muscle myoblasts upregulates myogenesis-related genes including MYOG, while ectopic AEBP1 expression suppresses these genes. TGF-β1 treatment upregulates AEBP1 and suppresses muscle differentiation genes. siRNA knockdown, ectopic AEBP1 overexpression, transcriptome analysis, qRT-PCR and western blot for myogenesis markers, TGF-β1 treatment, indirect co-culture with OSCC cells Scientific reports Medium 39521917

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome. American journal of human genetics 138 29606302
2010 Regulation of IkappaBalpha function and NF-kappaB signaling: AEBP1 is a novel proinflammatory mediator in macrophages. Mediators of inflammation 80 20396415
2010 PPARgamma1 and LXRalpha face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1. Nuclear receptor signaling 78 20419060
2020 AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways. Journal of oncology 62 32565808
2013 Aortic carboxypeptidase-like protein (ACLP) enhances lung myofibroblast differentiation through transforming growth factor β receptor-dependent and -independent pathways. The Journal of biological chemistry 61 24344132
2013 AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma. Cell death & disease 58 24201813
2021 Targeting of glioma stem-like cells with a parthenolide derivative ACT001 through inhibition of AEBP1/PI3K/AKT signaling. Theranostics 56 33391492
2019 AEBP1 expression increases with severity of fibrosis in NASH and is regulated by glucose, palmitate, and miR-372-3p. PloS one 48 31299062
2023 Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator. JCI insight 43 37917183
2019 Bi-allelic AEBP1 mutations in two patients with Ehlers-Danlos syndrome. Human molecular genetics 41 30668708
2005 The role of AEBP1 in sex-specific diet-induced obesity. Molecular medicine (Cambridge, Mass.) 40 16307171
2012 Identification of genomic targets of transcription factor AEBP1 and its role in survival of glioma cells. Molecular cancer research : MCR 37 22723309
2012 Stromal adipocyte enhancer-binding protein (AEBP1) promotes mammary epithelial cell hyperplasia via proinflammatory and hedgehog signaling. The Journal of biological chemistry 37 22995915
2022 Inhibition of AEBP1 predisposes cisplatin-resistant oral cancer cells to ferroptosis. BMC oral health 29 36352396
2021 Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease. Journal of translational medicine 29 34332599
2022 ACLP promotes activation of cancer-associated fibroblasts and tumor metastasis via ACLP-PPARγ-ACLP feedback loop in pancreatic cancer. Cancer letters 28 35732215
2011 Adipocyte enhancer-binding protein 1 (AEBP1) (a novel macrophage proinflammatory mediator) overexpression promotes and ablation attenuates atherosclerosis in ApoE (-/-) and LDLR (-/-) mice. Molecular medicine (Cambridge, Mass.) 28 21687917
1996 A cDNA cloning of human AEBP1 from primary cultured osteoblasts and its expression in a differentiating osteoblastic cell line. Biochemical and biophysical research communications 27 8920928
2019 AEBP1 Promotes the Occurrence and Development of Abdominal Aortic Aneurysm by Modulating Inflammation via the NF-κB Pathway. Journal of atherosclerosis and thrombosis 25 31462616
2019 Expanding the Clinical and Mutational Spectrum of Recessive AEBP1-Related Classical-Like Ehlers-Danlos Syndrome. Genes 24 30759870
2019 Association of AEBP1 and NRN1 RNA expression with Alzheimer's disease and neurofibrillary tangle density in middle temporal gyrus. Brain research 22 31176712
2019 AEBP1 down regulation induced cell death pathway depends on PTEN status of glioma cells. Scientific reports 19 31601918
2023 AEBP1 Contributes to Breast Cancer Progression by Facilitating Cell Proliferation, Migration, Invasion, and Blocking Apoptosis. Discovery medicine 18 37024441
2023 ACLP Activates Cancer-Associated Fibroblasts and Inhibits CD8+ T-Cell Infiltration in Oral Squamous Cell Carcinoma. Cancers 18 37686580
2019 Adipocyte enhancer binding protein 1 (AEBP1) knockdown suppresses human glioma cell proliferation, invasion and induces early apoptosis. Pathology, research and practice 17 31864713
2020 AEBP1 Promotes Glioblastoma Progression and Activates the Classical NF-κB Pathway. Behavioural neurology 16 33224311
2018 A biallelic truncating AEBP1 variant causes connective tissue disorder in two siblings. American journal of medical genetics. Part A 16 30548383
2023 Silencing of adipocyte enhancer-binding protein 1 (AEBP1) alleviates renal fibrosis in vivo and in vitro via inhibition of the β-catenin signaling pathway. Human cell 14 36738398
2021 LINC00511 knockdown suppresses glioma cell malignant progression through miR-15a-5p/AEBP1 axis. Brain research bulletin 13 33992709
2006 Modeling and functional analysis of AEBP1, a transcriptional repressor. Proteins 13 16538615
2011 Lactation defect with impaired secretory activation in AEBP1-null mice. PloS one 12 22114697
2024 AEBP1 promotes papillary thyroid cancer progression by activating BMP4 signaling. Neoplasia (New York, N.Y.) 10 38237535
2023 Case report: further delineation of AEBP1-related Ehlers-Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature. Frontiers in genetics 10 37214418
2021 AEBP1 Is One of the Epithelial-Mesenchymal Transition Regulatory Genes in Colon Adenocarcinoma. BioMed research international 9 34938806
2012 AEBP1 gene variants in infants with gastroschisis. Birth defects research. Part A, Clinical and molecular teratology 9 22821744
2025 AEBP1 or ACLP, which is the key factor in inflammation and fibrosis? International journal of biological macromolecules 7 40294683
2022 Congenital Defects in a Patient Carrying a Novel Homozygous AEBP1 Variant: Further Expansion of the Phenotypic Spectrum of Ehlers-Danlos Syndrome Classical-like Type 2? Genes 7 36553625
2019 Attenuating the abnormally high expression of AEBP1 suppresses the pathogenesis of childhood acute lymphoblastic leukemia via p53-dependent signaling pathway. European review for medical and pharmacological sciences 7 30779088
2025 AEBP1 drives fibroblast-mediated T cell dysfunction in tumors. Nature communications 6 40890191
2024 Clinical and Molecular Characterization of a Novel Homozygous Frameshift Variant in AEBP1-Related Classical-like Ehlers Danlos Syndrome Type 2 with Comparison to Previously Reported Rare Cases. Genes 6 38674395
2024 AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA-PI3K-Akt Axis. Drug development research 6 39670965
2026 Elucidating the Predominant Role of AEBP1 in Different Types of Cancers with a Focus on Glioblastoma Progression - A Review. Current gene therapy 5 40375702
2024 Dysregulated AEBP1 and COLEC12 Genes in Late-Onset Alzheimer's Disease: Insights from Brain Cortex and Peripheral Blood Analysis. Journal of molecular neuroscience : MN 5 38568322
2024 AEBP1 restores osteoblastic differentiation under dexamethasone treatment by activating PI3K/AKT signalling. Clinical and experimental pharmacology & physiology 5 39358837
2024 AEBP1 is a negative regulator of skeletal muscle cell differentiation in oral squamous cell carcinoma. Scientific reports 5 39521917
2023 The detailed obstetric course of the first Japanese patient with AEBP1-related Ehlers-Danlos syndrome (classical-like EDS, type 2). The journal of obstetrics and gynaecology research 5 36600409
2025 AEBP1 inhibition reduces cell growth and PI3K/AKT pathway while less regulates cell mobility in hepatocellular carcinoma. World journal of surgical oncology 4 40158165
2023 A single-chain variable fragment-anticancer lytic peptide (scFv-ACLP) fusion protein for targeted cancer treatment. Chemical biology & drug design 4 36862057
2021 Molecular Characterization of AEBP1 at Transcriptional Level in Glioma. BioMed research international 4 34373835
2024 Arenobufagin Induces Ferroptosis in Glioblastoma Cells via Modulating the MiR-149-5p/AEBP1 Axis. Journal of applied toxicology : JAT 3 39617010
2025 AEBP1 targets DDR2 to induce ferroptosis and microglial activation through the STAT3/P53 signaling pathway, exacerbating depression risk. Archives of biochemistry and biophysics 2 41083137
2025 Pan-Cancer Analysis Reveals AEBP1-Collagen Co-Expression and Its Potential Role in CAF-Mediated Tumor Stiffness. International journal of molecular sciences 2 41373631
2024 AEBP1 upregulation contributes to cervical cancer progression by facilitating cell proliferation, migration, and invasion. The journal of obstetrics and gynaecology research 2 38684171
2025 Silencing of AEBP1 inhibits proliferation and promotes apoptosis via the AKT signaling pathway in osteosarcoma. Biomedical reports 1 40502357
2025 AEBP1-GLI1 pathway attenuates the FACT complex dependency of bladder cancer cell survival. Biochemistry and biophysics reports 1 40612002
2025 AEBP1 as a promising therapeutic target for skeletal muscle insulin resistance in type 2 diabetes mellitus: Convergent evidence from Mendelian randomization and functional validation. Metabolism: clinical and experimental 1 40618921
2025 IL-32 positively regulates the AEBP1-IκBα-NF-κB-TNF-α axis to inhibit Mycobacterium tuberculosis infection in human macrophages. Microbial pathogenesis 1 40752529
2025 Integrative multi-omics analysis identifies AEBP1 and EFEMP2 as key regulators of immune heterogeneity and therapeutic response in glioblastoma. Discover oncology 1 41026376
2024 Clinical significance and potential mechanism of AEBP1 in glioblastoma. Journal of neuropathology and experimental neurology 1 39190880
2026 Targeting AEBP1 to Mitigate Protumor Activity of Cancer-Associated Fibroblasts and Increase Therapeutic Efficacy of Anti-PD-1. Molecular cancer therapeutics 0 41024581
2026 TWIST1-Mediated Induction of AEBP1 in Fibroblast-Like Synoviocytes Activates Transforming Growth Factor β Signaling to Drive Angiogenesis and Promote Rheumatoid Arthritis. Arthritis & rheumatology (Hoboken, N.J.) 0 41787682
2026 Astrocytic AEBP1-NPAS3-LIPA pathway coordinates cholesterol homeostasis to regulate Alzheimer's pathology. Cell reports 0 41880326
2026 Single-cell profiling and machine learning identify cuproptosis-related fibroblast subpopulations and fibrogenesis modulator AEBP1 in endometriosis. Apoptosis : an international journal on programmed cell death 0 42149287
2026 Gastrointestinal involvement in Ehlers-Danlos syndrome classical-like type 2 associated with a novel AEBP1 splice-site variant. Journal of human genetics 0 42191857
2026 Adipocyte Enhancer Binding Protein 1 (AEBP1) Inhibition as a Potential Anti-Fibrotic Therapy in Heart Failure. Research square 0 42245802
2025 Identification of foam cell like M2 macrophages, AEBP1 biomarkers, and resveratrol as potential therapeutic in MASLD using Ecotyper and WGCNA. Scientific reports 0 40825823
2025 Aebp1 loss in osteoprogenitors leads to skeletal defects resembling Ehlers-Danlos Syndrome by diminishing Wnt/β-catenin signaling. JCI insight 0 41231548
2013 Analysis of in vivo occupancy of Aebp1, a transcription factor, using high resolution tiling array. Methods in molecular biology (Clifton, N.J.) 0 23975792

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