Affinage

GREM1

Gremlin-1 · UniProt O60565

Length
184 aa
Mass
20.7 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GREM1 (Gremlin-1) is a secreted, dimeric cysteine-knot glycoprotein of the DAN family that functions principally as an extracellular antagonist of BMP2, BMP4, and BMP7, controlling BMP-dependent cell fate decisions across development, tissue homeostasis, and disease (PMID:10556075, PMID:27036124). It is synthesized as both glycosylated and non-glycosylated phosphorylated forms that localize to the ER/Golgi and the external cell surface, where both cell-associated and secreted protein bind BMP-4 and block its signaling (PMID:10722723). Structural and biophysical analysis shows GREM1 forms larger-than-1:1 oligomeric complexes with BMP-2 through a binding interface mapped on the ligand, defining a mode of inhibition distinct from Noggin and Chordin (PMID:27036124). In limb development GREM1 is the principal BMP antagonist sustaining the Shh(ZPA)-Fgf(AER) feedback loop, with its own expression tuned by BMP dose and spatially restricted by Shh (PMID:12808456, PMID:16989805); in kidney morphogenesis it acts downstream of Six1 and upstream of BMP4 to permit ureteric bud branching (PMID:21281623). In adult tissues GREM1 maintains homeostasis by attenuating BMP signaling near stem/progenitor niches: it marks and is required by skeletal osteochondroreticular stem cells, intestinal reticular stem cells, and articular cartilage progenitors, and its loss causes fatal enteropathy and bone marrow failure (PMID:25594183, PMID:32297672, PMID:37907525). Aberrant or stromally derived GREM1 disrupts the intestinal BMP gradient to reprogram non-stem progenitors and drive tumorigenesis, with expression driven by CDX2/TCF7L2 enhancer binding and by TGF-β in cancer-associated fibroblasts (PMID:25419707, PMID:25131200, PMID:31533776, PMID:33197448). Beyond BMP antagonism, GREM1 signals independently of BMPs: it binds VEGFR2 to activate Akt/mTORC2 and NF-κB-driven inflammation and angiogenesis (PMID:17077323, PMID:25810250, PMID:27894090), engages αvβ3 integrin to promote survival and migration (PMID:26834210), and modulates Smad2/3 (TGF-β) and Notch signaling to drive epithelial- and endothelial-to-mesenchymal transitions and fibrosis in kidney, pancreas, lung, and eye (PMID:19401426, PMID:26141517, PMID:29720422, PMID:32145252, PMID:26284554). GREM1 also binds SLIT1/SLIT2 in a glycosylation-dependent manner, mediating reciprocal negative cross-talk between the SLIT-ROBO and BMP-Gremlin pathways and inhibiting monocyte chemotaxis (PMID:15528323, PMID:29317497).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1999 High

    Established GREM1's foundational identity as a DAN-family BMP antagonist whose neutralization of BMP signaling controls limb outgrowth, apoptosis, and chondrogenesis, answering what this secreted protein does at the tissue level.

    Evidence Recombinant protein administration and in situ hybridization in chick limb bud

    PMID:10556075

    Open questions at the time
    • Did not resolve molecular stoichiometry of BMP binding
    • Mammalian genetic requirement not yet shown
  2. 2000 High

    Defined GREM1 as a secreted, glycosylated, phosphorylated glycoprotein present both at the cell surface and in the secretory pathway, with both forms competent to bind and block BMP-4, clarifying its biosynthesis and where it acts.

    Evidence Metabolic labeling, confocal immunofluorescence, 125I-BMP-4 binding and reporter assays

    PMID:10722723

    Open questions at the time
    • Functional role of phosphorylation unresolved
    • Structural basis of BMP binding not addressed
  3. 2003 High

    Demonstrated by mouse loss-of-function that GREM1 is genetically required to sustain the ZPA-AER feedback loop for limb patterning, moving from gain-of-function to in vivo necessity.

    Evidence Mouse knockout, skeletal phenotyping, allelic complementation with limb deformity mutation

    PMID:12808456

    Open questions at the time
    • Upstream regulation of Grem1 expression not defined here
  4. 2006 High

    Resolved the regulatory logic of Grem1 in the limb, showing BMP dose tunes its expression and Shh restricts its domain to terminate the signaling loop.

    Evidence Bead implantation, Shh-deficient mutants, cyclopamine blockade, limb mesenchyme culture

    PMID:16989805

    Open questions at the time
    • Direct transcriptional mediators not identified
    • Generalizability to other tissues untested
  5. 2006 High

    Revealed a BMP-independent proangiogenic function, the first evidence that GREM1 signals through receptors other than BMP ligands.

    Evidence Protein purification by endothelial sprouting, migration/invasion assays, CAM neovascularization, tyrosine phosphorylation

    PMID:17077323

    Open questions at the time
    • Endothelial receptor identity not yet defined
    • Intracellular signaling cascade only partly mapped
  6. 2004 Medium

    Identified SLIT1/SLIT2 as glycosylation-dependent GREM1/DAN binding partners and linked GREM1 to inhibition of monocyte chemotaxis, broadening its interactome beyond BMPs.

    Evidence Co-immunoprecipitation/pulldown, monocyte chemotaxis and competitive binding assays

    PMID:15528323

    Open questions at the time
    • Receptor mediating chemotaxis inhibition unknown
    • Single lab, in vitro binding
  7. 2002 Medium

    Provided early evidence that GREM1 overexpression can suppress tumorigenesis and induce p21 via a p53/MAPK-independent route, an effect later reframed against its pro-tumor stromal roles.

    Evidence Inducible/constitutive overexpression in tumor cell lines, Western blot, tumorigenicity assays

    PMID:12135612

    Open questions at the time
    • Mechanism of p21 transcriptional induction undefined
    • Apparent contradiction with later pro-tumor findings unresolved
  8. 2009 High

    Connected GREM1's BMP antagonism to disease, showing allelic depletion preserves renal pSmad1/5/8 and attenuates diabetic kidney injury, establishing GREM1 as a pathological BMP antagonist in fibrosis.

    Evidence Grem1+/- mice in streptozotocin diabetes, pSmad and fibrosis-marker readouts

    PMID:19401426

    Open questions at the time
    • Cell-type source of pathogenic Grem1 not pinpointed
    • Upstream induction signal unaddressed here
  9. 2011 High

    Placed GREM1 in a defined developmental hierarchy (Six1→Grem1→BMP4) required for ureteric bud branching, generalizing its BMP-antagonist role to kidney morphogenesis.

    Evidence Six1 knockout mice, GREM1 protein rescue, Six1/Bmp4 double-mutant epistasis, kidney rudiment culture

    PMID:21281623

    Open questions at the time
    • Direct transcriptional link Six1→Grem1 not shown
    • Restricted to renal development
  10. 2012 Medium

    Showed GREM1 binds cancer cells and drives migration, invasion, and EMT independently of BMP2/4/7 and VEGFR2, reinforcing a BMP-independent pro-tumor signaling arm.

    Evidence Cell binding, neutralizing antibody blocking, wound-healing/invasion assays, E-cadherin staining

    PMID:22514712

    Open questions at the time
    • Receptor mediating this binding not identified
    • Single lab in vitro
  11. 2015 High

    Identified VEGFR2 as a direct GREM1 receptor driving NF-κB-mediated renal inflammation independently of BMP antagonism, giving the proangiogenic/inflammatory arm a defined receptor.

    Evidence Recombinant gremlin in vivo/in vitro, VEGFR2 binding and kinase inhibition, NF-κB and histology

    PMID:25810250

    Open questions at the time
    • Stoichiometry of GREM1-VEGFR2 interaction undefined
    • Relationship to BMP-binding interface unmapped
  12. 2014 High

    Demonstrated that aberrant epithelial GREM1 disrupts the intestinal BMP gradient to confer stem-like properties on Lgr5-negative progenitors, defining a mechanism for GREM1-driven cancer initiation.

    Evidence HMPS patient tissue, mouse epithelial overexpression, BMP gradient mapping, Lgr5 lineage tracing

    PMID:25419707

    Open questions at the time
    • Quantitative BMP threshold for reprogramming not defined
    • Niche position dependence partly unresolved
  13. 2015 High

    Established GREM1 as a marker and functional requirement of skeletal/intestinal reticular stem cell populations, linking its niche-level BMP attenuation to multilineage stem cell maintenance.

    Evidence Grem1-Cre fate-mapping, clonal/transplantation assays, bone development and fracture-repair models

    PMID:25594183

    Open questions at the time
    • Whether Grem1 protein vs. Grem1+ cell is required separable only partly
    • Molecular niche signals upstream unclear
  14. 2016 High

    Provided the structural and biophysical basis of inhibition, showing GREM1 is a DAN-family dimer forming higher-order oligomers with BMP-2 by a mechanism distinct from Noggin/Chordin.

    Evidence X-ray crystallography, biolayer interferometry, BMP-2 mutagenesis

    PMID:27036124

    Open questions at the time
    • Structure of the GREM1-BMP complex not solved
    • Structural basis of BMP-independent receptor binding unknown
  15. 2018 Medium

    Extended BMP-independent signaling by showing GREM1 activates Notch (Jagged-1, N1ICD, hes-1/hey-1) linked to NF-κB renal inflammation, broadening the downstream effector repertoire.

    Evidence Tubular cell culture and in vivo gremlin injection, γ-secretase (DAPT) blockade, Western blot

    PMID:29720422

    Open questions at the time
    • Direct receptor coupling GREM1 to Notch not defined
    • Single lab
  16. 2018 High

    Defined direct SLIT2-GREM1 binding as a node of negative cross-talk between SLIT-ROBO and BMP-Gremlin pathways, with BMP/SMAD4 repressing SLIT2.

    Evidence Direct binding, SLIT2-ROBO2 neuron assay, BMP assays in myoblasts/fibroblasts, promoter and SMAD4 knockdown

    PMID:29317497

    Open questions at the time
    • Physiological context of this cross-talk in vivo unclear
    • Stoichiometry of SLIT2-GREM1 complex unmapped
  17. 2020 Medium

    Identified αvβ3 integrin as the receptor mediating GREM1-driven survival, proliferation, and invasion in synoviocytes via Erk/Akt/Bcl2, assigning a receptor to the integrin-engaging arm.

    Evidence siRNA, recombinant GREM1, αvβ3 neutralizing antibody, signaling Western blots and functional assays

    PMID:26834210

    Open questions at the time
    • Single lab, RA-FLS context
    • Direct GREM1-integrin binding not structurally defined
  18. 2020 Medium

    Showed GREM1 activates VEGFR2-Akt-mTORC2 in RPE cells to drive proliferation, migration, and VEGF production, refining the receptor-coupled signaling mechanism.

    Evidence SU5416, VEGFR2/Rictor/Sin1 knockdowns, p-Akt/mTORC2 Western blots, functional assays

    PMID:27894090

    Open questions at the time
    • Single lab
    • Cross-talk with BMP arm not assessed
  19. 2020 High

    Demonstrated that inducible Grem1 deletion in adult mice causes fatal enteropathy and bone marrow failure, proving an essential homeostatic requirement in epithelial renewal and hematopoiesis.

    Evidence Inducible conditional Grem1 knockout, histopathology, proliferation and marrow cellularity

    PMID:32297672

    Open questions at the time
    • Whether phenotype is fully BMP-dependent not dissected
    • Cellular source driving lethality not isolated
  20. 2021 High

    Showed stromal Grem1-mediated BMP attenuation is obligatory but submaximal for regenerative stem-cell reprogramming after intestinal injury, refining its role in tissue regeneration.

    Evidence Transgenic autocrine Bmp4 and Grem1 deletion/overexpression mice, spatial BMP mapping in human and mouse

    PMID:33819486

    Open questions at the time
    • Quantitative interplay with YAP/TAZ not fully resolved
    • Fibroblast subpopulation specificity partly open
  21. 2021 High

    Identified Grem1+ fibroblastic reticular cells as niche cells required for dendritic cell homeostasis and T-cell immunity, extending GREM1+ stromal niche function to immunity.

    Evidence Human/mouse scRNA-seq, Grem1-CreERT2 depletion, flow cytometry, T-cell immunity assays

    PMID:33903764

    Open questions at the time
    • Whether Grem1 protein itself is the mediator vs. cell identity not separated
    • Receptor on cDCs undefined
  22. 2019 Medium

    Established a TGF-β→CAF-Grem1→BMP/SMAD axis driving breast cancer stemness, EMT, and dissemination, integrating stromal regulation with tumor cell phenotype.

    Evidence In situ hybridization, recombinant protein, SMAD assays, functional assays, zebrafish xenograft

    PMID:31533776

    Open questions at the time
    • Single lab
    • Direct receptor on tumor cells not defined here
  23. 2020 Medium

    Linked GREM1 to metastatic signaling through STAT3-driven MMP13 transcription, adding a downstream transcriptional effector for its pro-metastatic activity.

    Evidence Knockdown/overexpression, orthotopic mouse model, STAT3 and MMP13 readouts

    PMID:33287358

    Open questions at the time
    • Receptor upstream of STAT3 not identified
    • Single lab
  24. 2014 High

    Showed GREM1 is a direct transcriptional target of CDX2 and the Wnt effector TCF7L2 at a CRC risk allele, mechanistically connecting genetic risk to elevated GREM1 and tumor burden.

    Evidence Enhancer reporter, allele-specific CDX2/TCF7L2 binding, CDX2 overexpression, ApcMin dosage model

    PMID:25131200

    Open questions at the time
    • Tissue-specificity of enhancer activity in vivo only partly resolved
  25. 2022 High

    Demonstrated bidirectionally (KO and OE in established PDAC) that paracrine Grem1 suppresses Snail/Slug to maintain epithelial identity and tumor cell heterogeneity, a striking cell-fate stabilizing role.

    Evidence Conditional Grem1 KO and OE in mouse PDAC, time-course fate analysis, human validation

    PMID:35768509

    Open questions at the time
    • Receptor mediating epithelial response not defined
    • Whether purely BMP-mediated not fully isolated
  26. 2022 High

    Defined GREM1/ISLR as antagonistic CAF-derived regulators of stromal BMP signaling in CRC, with GREM1 neutralization or ISLR delivery suppressing tumor growth and promoting stem-cell differentiation.

    Evidence Human CRC RNA, in situ hybridization, tumoroid + neutralizing antibody, Islr overexpression, AAV8 in vivo

    PMID:33197448

    Open questions at the time
    • Mechanism of FOXL1/TGF-β control of subpopulations partly open
  27. 2022 High

    Showed GREM1 marks bipotent articular cartilage progenitors whose depletion causes OA, with Foxo1 required for their survival and FGF18/FGFR3 promoting their expansion, defining a regenerative target in joint disease.

    Evidence Grem1-Cre lineage tracing, genetic ablation, Foxo1 conditional KO, FGF18 administration, transcriptomics

    PMID:37907525

    Open questions at the time
    • Whether Grem1 protein vs. Grem1+ cell drives chondroprotection not separated
  28. 2022 Medium

    Implicated GREM1 across fibrotic and degenerative diseases through differential Smad balance, antagonizing protective BMP and modulating TGF-β/Smad2/3 in lung EndMT, disc apoptosis, ocular hypertension, and NASH senescence.

    Evidence Recombinant protein and knockdown studies, Smad phosphorylation, Smad3-KO epistasis, spheroid and in vivo models

    PMID:26141517 PMID:26284554 PMID:32145252 PMID:35440754 PMID:35995996

    Open questions at the time
    • Receptor specificity for TGF-β/Smad2/3 effects not defined
    • Cross-tissue generalizability uncertain

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GREM1's BMP-antagonist surface relates structurally to its BMP-independent receptor engagements (VEGFR2, αvβ3 integrin, SLIT2) and how a single secreted factor selects among these outputs in a given tissue remains unresolved.
  • No structure of GREM1 with any non-BMP receptor
  • Determinants of context-dependent BMP-dependent vs. -independent signaling unknown
  • Reconciliation of tumor-suppressive vs. pro-tumor activities incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0048018 receptor ligand activity 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005576 extracellular region 3 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-1474244 Extracellular matrix organization 2
Partners
BMP2BMP4BMP7ITGAVITGB3SLIT1SLIT2VEGFR2

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Gremlin is a member of the DAN family of BMP antagonists that binds and blocks BMP2, BMP4, and BMP7; exogenous recombinant Gremlin in the developing avian limb controls outgrowth, restricts programmed cell death, confines chondrogenesis, and regulates interdigital tissue regression, all mediated by neutralization of BMP signaling. In vivo administration of recombinant protein in chick embryo limb bud; expression analysis by in situ hybridization Development High 10556075
2000 Drm/Gremlin is synthesized as a secreted glycoprotein that exists in both glycosylated and non-glycosylated forms; both undergo phosphorylation. The protein is present on the external cell surface and within the ER/Golgi. Both cell-associated and secreted forms bind 125I-BMP-4 and antagonize BMP signaling. Metabolic labeling, SDS-PAGE, confocal immunofluorescence microscopy, 125I-BMP-4 binding assay, BMP signaling reporter assay Journal of Biological Chemistry High 10722723
2003 Gremlin (Cktsf1b1) is the principal BMP antagonist required for early limb outgrowth and patterning in mice; its loss interrupts the positive feedback loop between the zone of polarizing activity (ZPA/Shh) and the apical ectodermal ridge (AER/Fgf), resulting in abnormal skeletal patterning. The gremlin mutation is allelic to the limb deformity (ld) mutation. Mouse knockout/genetic mutation, in vivo skeletal phenotyping, genetic epistasis (allele complementation) Nature Genetics High 12808456
2002 Drm/Gremlin overexpression in tumor-derived cell lines (Daoy, Saos-2) inhibits tumorigenesis, increases p21(Cip1) protein levels via a p53- and MAP kinase-independent transcriptional mechanism, and reduces phospho-p42/44 MAP kinase levels. Ecdysone-inducible and constitutive overexpression in tumor cell lines; Western blot for p21(Cip1) and phospho-p42/44 MAPK; tumorigenicity assays Biochemical and Biophysical Research Communications Medium 12135612
2004 Drm/Gremlin and Dan physically interact with Slit1 and Slit2 proteins; this binding depends on glycosylation of Drm and is not competed by BMPs. Drm and Dan function as inhibitors of monocyte chemotaxis induced by SDF-1α or fMLP; Dan's inhibition is not due to blocking SDF-1α binding to its receptor. Co-immunoprecipitation/pulldown, monocyte chemotaxis assays, competitive binding assays Journal of Immunology Medium 15528323
2006 Drm/Gremlin is a proangiogenic factor expressed by endothelium that stimulates endothelial cell migration and invasion in fibrin and collagen gels, binds with high affinity to endothelial cells, triggers tyrosine phosphorylation of intracellular signaling proteins, and induces neovascularization in the chick chorioallantoic membrane. This proangiogenic activity is BMP4-independent: BMP4 does not affect Drm/Gremlin–endothelium interaction. Protein purification from conditioned medium using endothelial sprouting assay; recombinant protein binding studies; in vitro migration/invasion assays; CAM neovascularization assay; tyrosine phosphorylation Western blot Blood High 17077323
2006 BMP activity is necessary and sufficient for induction of Gremlin expression in the posterior limb bud (low BMP2 upregulates Gremlin; high BMP2 downregulates it). Shh activity is required to exclude Gremlin from the posterior limb domain, thereby terminating the Shh-Fgf4 signaling loop. Bead implantation assays (BMP2, Noggin beads in chick limb), oligozeugodactyly mutant limbs lacking Shh, cyclopamine Shh blockade, in vivo limb mesenchyme cultures Developmental Biology High 16989805
2007 Gremlin promotes vascular smooth muscle cell (VSMC) proliferation and migration by blocking BMP signaling; stable overexpression blocks BMP-induced reduction of DNA synthesis, accelerates cell cycle progression through p27(kip1) down-regulation, and increases migration. Gremlin expression in VSMCs is induced by angiotensin II, TGF-β1, and PDGF, and is elevated in neointima of balloon-injured carotid arteries. Stable overexpression, gene silencing (siRNA), DNA synthesis assay, cell counting, cell cycle analysis, migration assay, in vivo balloon injury model, Western blot Journal of Molecular and Cellular Cardiology Medium 18086474
2009 Allelic depletion of grem1 in streptozotocin-diabetic mice (grem1+/-) attenuates diabetic kidney disease: pSmad1/5/8 (BMP signaling) is maintained in grem1+/- kidneys (unlike wild-type diabetic kidneys), and markers of renal damage (fibronectin, CTGF, glomerular basement membrane thickening, microalbuminuria) are reduced, placing grem1 as a BMP antagonist driving renal injury. Grem1 heterozygous knockout mouse, streptozotocin diabetes model, immunohistochemistry, Western blot for pSmad1/5/8 and fibrosis markers, microalbuminuria measurement Diabetes High 19401426
2011 Six1 regulates Grem1 expression in the metanephric mesenchyme (MM) to initiate ureteric bud branching morphogenesis: Six1-/- mice lack Grem1 expression in the MM, causing failure of ampulla formation. Restoring GREM1 protein to Six1-/- kidney rudiments rescues branching. Genetic reduction of BMP4 in Six1-/- mice (Six1-/-; Bmp4+/-) also restores urinary tract morphogenesis, placing Grem1 downstream of Six1 and upstream of BMP4 in this pathway. Six1 knockout mice, GREM1 protein rescue experiment, genetic epistasis (Six1-/-; Bmp4+/- double mutant), in vitro kidney rudiment culture Developmental Biology High 21281623
2012 Gremlin-1 binds various cancer cell lines independently of BMP-2, BMP-4, BMP-7, and VEGFR2. This BMP-independent binding promotes cell migration, invasion, proliferation, and EMT (decreased E-cadherin), all of which are blocked by a neutralizing anti-gremlin-1 antibody (GRE1). Cell binding assays, antibody blocking, scratch wound healing assay, invasion assay, stable gremlin-1 transfection, E-cadherin immunostaining PLoS ONE Medium 22514712
2015 Gremlin (VEGFR2 agonist) binds to VEGFR2 in renal proximal tubular epithelial cells and activates VEGFR2 signaling independently of its BMP antagonism. In vivo administration of recombinant gremlin to murine kidneys activates VEGFR2 signaling and triggers NF-κB-driven renal inflammation and immune cell infiltration; VEGFR2 blockade diminishes these effects. Recombinant gremlin administration in vivo and in vitro, VEGFR2 binding assay, VEGFR2 kinase inhibitor treatment, co-immunoprecipitation/binding in tubular cells, NF-κB activation by Western blot, histological analysis of inflammatory infiltrate Journal of Pathology High 25810250
2015 Gremlin 1 defines a skeletal stem cell population (osteochondroreticular, OCR) in bone marrow metaphysis that self-renews and gives rise to osteoblasts, chondrocytes, and reticular marrow stromal cells (but not adipocytes); Grem1 expression is required for bone development, bone remodeling, and fracture repair. Grem1 also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Gremlin-1-Cre fate-mapping in mice, clonal analysis, in vivo bone development and fracture repair models, flow cytometry, transplantation assays Cell High 25594183
2015 Gremlin 1 (along with FRZB and DKK1) inhibits hypertrophic differentiation of human articular chondrocytes, maintaining cartilage homeostasis. Supplementation of these proteins diminishes terminal hypertrophic differentiation without affecting chondrogenesis in long-bone explant cultures and in chondrogenically differentiating human MSCs. Recombinant protein supplementation in long-bone explant cultures and human MSC chondrogenic differentiation; gene expression profiling; whole-genome microarray Arthritis and Rheumatism Medium 22576962
2015 Gremlin induces ocular hypertension in mice via Smad3-dependent signaling in the trabecular meshwork (TM): intravitreal Ad5.Gremlin elevates IOP and upregulates fibronectin and collagen-1 expression in TM of Smad3 wild-type but not Smad3 HET or KO mice. Gremlin and TGFβ2 reciprocally increase each other's expression in the TM. Intravitreal adenoviral injection in wild-type vs. Smad3 knockout mice, IOP measurement, Western blot, immunofluorescence, qPCR Investigative Ophthalmology & Visual Science High 26284554
2015 Gremlin 1 is a key pro-fibrogenic factor in chronic pancreatitis: TGF-β induces Grem1 expression in pancreatic stellate cells; Grem1 blocks BMP2-induced Smad1/5 phosphorylation and abolishes BMP2's suppression of TGF-β-induced collagen expression. Grem1+/- mice show ~33% reduction in pancreatic fibrosis. Mouse CP model (cerulein), Grem1+/- knockout mice, isolated pancreatic stellate cell cultures, recombinant Grem1 protein treatment, Smad1/5 phosphorylation Western blot, collagen quantification Journal of Molecular Medicine High 26141517
2016 Crystal structure of Gremlin-1 reveals a conserved dimeric structure similar to other DAN family inhibitors. Biophysical analysis shows Gremlin-1 and BMP-2 form larger oligomeric complexes beyond 1:1 stoichiometry. Mutagenesis mapped the Gremlin-1 binding site on BMP-2, revealing a mechanism of BMP inhibition distinct from Noggin and Chordin. X-ray crystallography (crystal structure of Gremlin-1), biolayer interferometry (BLI) binding kinetics, site-directed mutagenesis of BMP-2 Biochemical Journal High 27036124
2016 GREM1 is a direct transcriptional target of CDX2 and TCF7L2 (Wnt effector): the CRC risk allele at rs16969681 lies in active chromatin with enhancer activity; CDX2 and TCF7L2 bind this region with higher affinity for the risk allele, driving stronger GREM1 expression. Higher Grem1 mRNA increases intestinal tumor burden in ApcMin mice. Chromatin accessibility/enhancer reporter assay, allele-specific CDX2/TCF7L2 binding assay, CDX2 overexpression-driven GREM1 re-expression, ApcMin mouse model with Grem1 dosage manipulation Cell Reports High 25131200
2018 Gremlin activates the Notch signaling pathway in kidney tubular cells: recombinant gremlin upregulates Jagged-1, induces nuclear translocation of active Notch-1 (N1ICD), and upregulates Notch effectors hes-1 and hey-1 in vitro and in vivo. This Notch activation is linked to NF-κB-mediated renal inflammation. In vitro tubular cell culture, in vivo murine renal gremlin injection, γ-secretase inhibitor (DAPT) Notch blockade, Western blot for N1ICD, gene expression analysis Clinical Science Medium 29720422
2018 SLIT2 and Gremlin interact directly: the SLIT2-Gremlin interaction inhibits both SLIT2-ROBO2 signaling in neurons and Gremlin antagonism of BMP activity in myoblasts and fibroblasts. BMP2 down-regulates SLIT2 expression through canonical BMP/SMAD4 signaling; Gremlin treatment, BMP receptor inhibition, or SMAD4 knockdown rescues SLIT2 repression—revealing negative cross-talk between the SLIT2 and BMP-Gremlin pathways. Direct binding assays, SLIT2-ROBO2 signaling assay in neurons, BMP activity assay in myoblasts/fibroblasts, SLIT2 promoter activity assay, SMAD4 knockdown, BMP receptor inhibition Journal of Biological Chemistry High 29317497
2019 Cancer-associated fibroblast (CAF)-derived Grem1 abrogates BMP/SMAD signaling in breast cancer cells, promoting mesenchymal phenotype, stemness, and invasion. TGF-β secreted by breast cancer cells stimulates GREM1 expression in CAFs. Grem1 also promotes fibrogenic activation of CAFs and breast cancer cell intravasation and extravasation in zebrafish xenograft models. In situ hybridization, recombinant protein treatment, SMAD signaling assay, functional cell-based assays (stemness, invasion), collagen contraction assay, zebrafish xenograft co-injection model Breast Cancer Research Medium 31533776
2020 GREM1 promotes breast cancer cell metastasis by activating STAT3, which drives MMP13 transcription. GREM1 knockdown reduces tumor growth and lung metastasis in an orthotopic mouse model. GREM1 knockdown/overexpression, orthotopic mouse model, STAT3 activation assay, MMP13 expression analysis, migration/invasion assays International Journal of Molecular Sciences Medium 33287358
2020 Gremlin-1 activates VEGFR2-Akt-mTORC2 signaling in retinal pigment epithelial (RPE) cells to promote cell proliferation, migration, and VEGF production; VEGFR2 inhibition or knockdown, and mTORC2 component knockdown (Rictor, Sin1), abolished these effects. Pharmacological inhibition (SU5416), shRNA knockdown of VEGFR2/mTORC2 components, Western blot for p-Akt/mTORC2, proliferation/migration assays, VEGF ELISA Oncotarget Medium 27894090
2020 GREM1 in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) promotes cell proliferation, survival, migration, and invasion via αvβ3 integrin signaling: GREM1 siRNA reduces pErk1/2, pAkt, and Bcl2 while increasing Bax expression; these effects are completely blocked by anti-αvβ3 integrin neutralizing antibodies. siRNA knockdown, recombinant GREM1 treatment, αvβ3 integrin neutralizing antibody, Western blot for signaling proteins, cell proliferation/migration/invasion assays Journal of Rheumatology Medium 26834210
2020 GREM1 activates Akt/STAT3 signaling to increase glycolysis in breast cancer cells by upregulating hexokinase-2 (HK2) expression; this operates via a ROS-Akt-STAT3 axis and increases glucose uptake and lactate production. GREM1 overexpression, glucose uptake/lactate production assays, Western blot for STAT3/Akt/HK2, ROS measurement, signaling inhibitors Biochemical and Biophysical Research Communications Low 33097188
2021 Stromal Grem1 upregulation from topographically distinct fibroblast populations is required for adaptive BMP pathway attenuation during intestinal regeneration after ulceration; this Grem1-mediated BMP antagonism is obligatory but functionally submaximal for regenerative stem cell reprogramming. Mechanistically, BMP pathway activation (via Bmp4) abrogates regenerative stem cell dedifferentiation despite convergent YAP/TAZ effects on cell fate. Novel mouse model (autocrine Bmp4 ligand), spatial BMP signaling mapping (mouse and human), Grem1 deletion transgenic mice, Bmp4 or Grem1 epithelial overexpression, intestinal regeneration assays Gastroenterology High 33819486
2021 Grem1+ fibroblastic reticular cells (FRCs) localize at T-B cell junctions in secondary lymphoid organs and are required for homeostatic maintenance of resident conventional dendritic cells (cDCs): Grem1+ FRC depletion causes preferential loss, decreased homeostatic proliferation and survival of cDCs, and compromised T cell immunity. scRNA-seq (human and mouse lymph nodes), Grem1-CreERT2 knock-in mice for genetic depletion, multi-omics characterization, flow cytometry, functional T cell immunity assays Nature Immunology High 33903764
2022 Grem1 inhibits the expression of EMT transcription factors Snai1 (Snail) and Snai2 (Slug) in epithelial PDAC cells, maintaining epithelial identity by suppressing BMP activity. Grem1 inactivation in established PDAC causes direct conversion of epithelial to mesenchymal cells; conversely, Grem1 overexpression causes epithelialization of mesenchymal PDAC cells. This paracrine mechanism (Grem1 expressed in mesenchymal cells, acting on epithelial cells) is required to maintain cellular heterogeneity in pancreatic cancer. Conditional Grem1 knockout in established PDAC mouse tumors, Grem1 overexpression in mesenchymal PDAC cells, time-course cell fate analysis, Snai1/Snai2 expression analysis, human PDAC validation Nature High 35768509
2022 Grem1 accelerates nucleus pulposus cell apoptosis in intervertebral disc degeneration by inhibiting TGF-β-mediated Smad2/3 phosphorylation: Grem1 siRNA reduces apoptosis in TNF-α-induced degenerative NP cells and inhibits IVDD progression in vivo. siRNA knockdown, flow cytometry for apoptosis, Western blot for p-Smad2/3, immunofluorescence, in vivo IVDD rat model with local siRNA injection Experimental & Molecular Medicine Medium 35440754
2020 Grem1 depletion in adult mice causes fatal enteropathy (failure of epithelial cell replication and maturation, villous atrophy) and bone marrow failure with haematopoietic insufficiency, demonstrating an essential homeostatic role for Grem1 in maintaining intestinal epithelial renewal and haematopoiesis. Inducible Grem1 conditional knockout (ROSA26CreER-Grem1flx/flx) in adult mice, tamoxifen induction, histopathology, assessment of epithelial proliferation and bone marrow cellularity Journal of Pathology High 32297672
2022 GREM1 and ISLR are CAF-specific genes that antagonistically regulate stromal BMP signaling in colorectal cancer: GREM1 inhibits BMP signaling while ISLR promotes it. They mark distinct fibroblast subpopulations differentially regulated by TGF-β and FOXL1. GREM1-neutralizing antibody or fibroblast Islr overexpression reduces CRC tumoroid growth and promotes Lgr5+ stem cell differentiation. AAV8-mediated Islr delivery to hepatocytes increased BMP signaling and improved survival in a mouse liver metastasis model. Human CRC RNA analysis, in situ hybridization, CRC tumoroid assays with GREM1-neutralizing antibody, fibroblast Islr overexpression, AAV8 gene delivery in mouse hepatic metastasis model, BMP signaling assays Gastroenterology High 33197448
2022 Gremlin-1 induces endothelial-to-mesenchymal transition (EndMT) in pulmonary artery endothelial cells (PAECs) via phospho-Smad2/3-dependent signaling; BMP-7 reverses Gremlin-1-induced EndMT by inducing phospho-Smad1/5/8 and suppressing phospho-Smad2/3. Recombinant gremlin-1 treatment, BMP-7 treatment, immunofluorescence for EndMT markers (α-SMA, VWF), Western blot for Smad phosphorylation, migration and tube formation assays Experimental Cell Research Medium 32145252
2022 In NAFLD/NASH, Gremlin 1 (expressed highly in visceral fat) is pro-senescent and antagonistic to BMP4. BMP4 is anti-senescent, anti-steatotic, anti-inflammatory and anti-fibrotic in liver cell spheroids. Both senescence and anti-senescence factors target the YAP/TAZ pathway in this context. Human liver biopsies (n=58), liver cell spheroids (stellate and hepatocyte cells), recombinant BMP4 and Gremlin 1 treatment, senescence markers, YAP/TAZ pathway assays, machine learning analysis Nature Metabolism Medium 35995996
2014 Aberrant epithelial GREM1 expression (caused by the HMPS duplication) disrupts homeostatic intestinal BMP morphogen gradients, alters cell fate along the vertical epithelial axis, and promotes persistence/reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche, enabling ectopic crypt formation and cancer initiation from non-stem cells. HMPS patient tissue analysis, mouse model of GREM1 epithelial overexpression, BMP gradient mapping, Lgr5 lineage tracing, histology, somatic mutation analysis Nature Medicine High 25419707
2023 Grem1 marks a bipotent chondrogenic/osteogenic progenitor cell population within the articular surface; these progenitors are depleted by injury-induced OA and aging, and their genetic ablation causes OA in mice. Foxo1 is required for Grem1-lineage cell survival (Foxo1 ablation in Grem1-lineage cells causes OA). FGFR3 pathway activation by FGF18 drives Grem1-lineage chondrocyte progenitor proliferation, increases cartilage thickness, and reduces OA. Grem1-Cre lineage tracing, genetic cell ablation in mice, Foxo1 conditional knockout in Grem1-lineage cells, FGF18 administration, transcriptomic analysis, OA scoring Nature Communications High 37907525

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential. Cell 543 25594183
2002 Locus-specific control of asymmetric and CpNpG methylation by the DRM and CMT3 methyltransferase genes. Proceedings of the National Academy of Sciences of the United States of America 415 12151602
2003 Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation. Current biology : CB 369 14680640
2003 Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nature genetics 295 12808456
1999 The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb. Development (Cambridge, England) 267 10556075
2007 Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk. Nature genetics 246 18084292
2014 Molecular mechanism of action of plant DRM de novo DNA methyltransferases. Cell 240 24855943
2014 Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nature medicine 216 25419707
2012 Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nature genetics 184 22561515
2011 Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS genetics 182 21655089
2020 The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis. Gastroenterology 131 33197448
2019 Cancer-associated fibroblast-derived Gremlin 1 promotes breast cancer progression. Breast cancer research : BCR 130 31533776
2018 LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 127 30120709
2000 Biosynthesis, post-translation modification, and functional characterization of Drm/Gremlin. The Journal of biological chemistry 122 10722723
2005 Expression of gremlin, a bone morphogenetic protein antagonist, in human diabetic nephropathy. American journal of kidney diseases : the official journal of the National Kidney Foundation 120 15957132
2012 Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis. Arthritis and rheumatism 114 22576962
2006 Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor. Blood 114 17077323
1997 Identification of drm, a novel gene whose expression is suppressed in transformed cells and which can inhibit growth of normal but not transformed cells in culture. Molecular and cellular biology 107 9234736
2016 miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1. Scientific reports 105 27910957
2007 Co-regulation of Gremlin and Notch signalling in diabetic nephropathy. Biochimica et biophysica acta 92 17980714
2022 Grem1 accelerates nucleus pulposus cell apoptosis and intervertebral disc degeneration by inhibiting TGF-β-mediated Smad2/3 phosphorylation. Experimental & molecular medicine 91 35440754
2021 Gremlin 1+ fibroblastic niche maintains dendritic cell homeostasis in lymphoid tissues. Nature immunology 80 33903764
2005 DNA methylation-associated inactivation of TGFbeta-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers. British journal of cancer 71 16234815
2003 An ancestral Ashkenazi haplotype at the HMPS/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome. American journal of human genetics 71 12696020
2022 GREM1 is required to maintain cellular heterogeneity in pancreatic cancer. Nature 69 35768509
2013 GREM1, FRZB and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-associated factors. Arthritis research & therapy 69 24286177
2022 BMP4 and Gremlin 1 regulate hepatic cell senescence during clinical progression of NAFLD/NASH. Nature metabolism 68 35995996
2016 Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene. PLoS genetics 68 26968009
2009 Allelic depletion of grem1 attenuates diabetic kidney disease. Diabetes 67 19401426
2016 Structure of Gremlin-1 and analysis of its interaction with BMP-2. The Biochemical journal 61 27036124
2009 Role of gremlin in the lung: development and disease. American journal of respiratory cell and molecular biology 60 19574532
2004 Cutting edge: bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with Slits and act as negative regulators of monocyte chemotaxis. Journal of immunology (Baltimore, Md. : 1950) 60 15528323
2006 Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function. Journal of medical genetics 57 16525031
2006 Regulation of Gremlin expression in the posterior limb bud. Developmental biology 56 16989805
2020 Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway. International journal of molecular sciences 54 33287358
2015 Bone morphogenetic protein antagonist gremlin-1 regulates colon cancer progression. Biological chemistry 54 25153376
2012 Gremlin-1 induces BMP-independent tumor cell proliferation, migration, and invasion. PloS one 53 22514712
2000 DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain. Cytogenetics and cell genetics 53 10894942
2015 Gremlin regulates renal inflammation via the vascular endothelial growth factor receptor 2 pathway. The Journal of pathology 52 25810250
2002 Drm/Gremlin transcriptionally activates p21(Cip1) via a novel mechanism and inhibits neoplastic transformation. Biochemical and biophysical research communications 48 12135612
2002 Gremlin: an example of the re-emergence of developmental programmes in diabetic nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 48 12386293
2021 Bone Morphogenetic Protein Pathway Antagonism by Grem1 Regulates Epithelial Cell Fate in Intestinal Regeneration. Gastroenterology 46 33819486
2011 Chromosome-biased binding and gene regulation by the Caenorhabditis elegans DRM complex. PLoS genetics 46 21589891
2007 Expression of gremlin, a bone morphogenetic protein antagonist, in glomerular crescents of pauci-immune glomerulonephritis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 45 17403698
2007 Gremlin promotes vascular smooth muscle cell proliferation and migration. Journal of molecular and cellular cardiology 44 18086474
2015 Gremlin is a key pro-fibrogenic factor in chronic pancreatitis. Journal of molecular medicine (Berlin, Germany) 43 26141517
2015 GREMLIN 2 Mutations and Dental Anomalies. Journal of dental research 42 26416033
2014 A polymorphic enhancer near GREM1 influences bowel cancer risk through differential CDX2 and TCF7L2 binding. Cell reports 42 25131200
2015 GREM1 and POLE variants in hereditary colorectal cancer syndromes. Genes, chromosomes & cancer 38 26493165
2010 A GREM1 gene variant associates with diabetic nephropathy. Journal of the American Society of Nephrology : JASN 37 20150533
2017 GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas. PloS one 35 28346486
2014 Roles of Gremlin 1 and Gremlin 2 in regulating ovarian primordial to primary follicle transition. Reproduction (Cambridge, England) 35 24614542
2023 Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis. Nature communications 34 37907525
2018 Gremlin activates the Notch pathway linked to renal inflammation. Clinical science (London, England : 1979) 33 29720422
2018 Knockdown GREM1 suppresses cell growth, angiogenesis, and epithelial-mesenchymal transition in colon cancer. Journal of cellular biochemistry 32 30426548
2003 The Drm-Bowl-Lin relief-of-repression hierarchy controls fore- and hindgut patterning and morphogenesis. Mechanisms of development 31 14568103
2015 Gremlin Induces Ocular Hypertension in Mice Through Smad3-Dependent Signaling. Investigative ophthalmology & visual science 30 26284554
2022 Gremlin-1 Promotes Colorectal Cancer Cell Metastasis by Activating ATF6 and Inhibiting ATF4 Pathways. Cells 29 35883579
2016 GREM1, EGFR, and HAS2; the oocyte competence markers for improved buffalo embryo production in vitro. Theriogenology 29 27448692
2021 He-Chan Pian inhibits the metastasis of non-small cell lung cancer via the miR-205-5p-mediated regulation of the GREM1/Rap1 signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 28 34752967
2019 Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial-mesenchymal transition by suppressing the TGF-β/smad pathway via binding to GREM1. Cancer cell international 28 31143092
2019 Gremlin is a potential target for posterior capsular opacification. Cell cycle (Georgetown, Tex.) 28 31234714
2017 Gremlin-1 is a key regulator of the invasive cell phenotype in mesothelioma. Oncotarget 28 29228689
2016 BMP signalling in human fetal ovary somatic cells is modulated in a gene-specific fashion by GREM1 and GREM2. Molecular human reproduction 28 27385727
2011 Six1 regulates Grem1 expression in the metanephric mesenchyme to initiate branching morphogenesis. Developmental biology 28 21281623
2009 Bone morphogenetic protein-7 and Gremlin: New emerging therapeutic targets for diabetic nephropathy. Biochemical and biophysical research communications 27 19303394
2022 GREM1/PPP2R3A expression in heterogeneous fibroblasts initiates pulmonary fibrosis. Cell & bioscience 26 35933397
2020 Circ_DHRS3 positively regulates GREM1 expression by competitively targeting miR-183-5p to modulate IL-1β-administered chondrocyte proliferation, apoptosis and ECM degradation. International immunopharmacology 26 33360372
2016 Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling. Oncotarget 26 27713170
2016 GREM1 Is a Key Regulator of Synoviocyte Hyperplasia and Invasiveness. The Journal of rheumatology 25 26834210
2020 GREM1 inhibits osteogenic differentiation, senescence and BMP transcription of adipose-derived stem cells. Connective tissue research 23 32151168
2004 Drm/Gremlin, a BMP antagonist, defines the interbud region during feather development. The International journal of developmental biology 23 15272379
2018 Overexpression of Gremlin 1 by sonic hedgehog signaling promotes pancreatic cancer progression. International journal of oncology 22 30272371
2011 Impaired gremlin 1 (GREM1) expression in cumulus cells in young women with diminished ovarian reserve (DOR). Journal of assisted reproduction and genetics 22 22160428
2020 DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells. Bioscience reports 21 32141512
2018 Gremlin and renal diseases: ready to jump the fence to clinical utility? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 21 28992340
2018 Cenani-Lenz syndrome and other related syndactyly disorders due to variants in LRP4, GREM1/FMN1, and APC: Insight into the pathogenesis and the relationship to polyposis through the WNT and BMP antagonistic pathways. American journal of medical genetics. Part A 20 30569497
2017 Gremlin promotes retinal pigmentation epithelial (RPE) cell proliferation, migration and VEGF production via activating VEGFR2-Akt-mTORC2 signaling. Oncotarget 20 27894090
2017 Gremlin-1 suppression increases BMP-2-induced osteogenesis of human mesenchymal stem cells. Molecular medicine reports 20 28260028
2022 Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes. International journal of molecular sciences 19 35216203
2020 Gremlin-1 activates Akt/STAT3 signaling, which increases the glycolysis rate in breast cancer cells. Biochemical and biophysical research communications 19 33097188
2018 Identification of direct negative cross-talk between the SLIT2 and bone morphogenetic protein-Gremlin signaling pathways. The Journal of biological chemistry 19 29317497
2001 Expression pattern of the drm/gremlin gene during chicken embryonic development. Mechanisms of development 19 11231088
2024 miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. Cancer cell international 18 38970064
2020 Gremlin-1 is a key regulator of endothelial-to-mesenchymal transition in human pulmonary artery endothelial cells. Experimental cell research 18 32145252
2008 Isolation and expression analysis of genes encoding MET, CMT, and DRM methyltransferases in oil palm (Elaeis guineensis Jacq.) in relation to the 'mantled' somaclonal variation. Journal of experimental botany 18 18640997
2005 Differential expression of the peripheral benzodiazepine receptor and gremlin during adipogenesis. Obesity research 18 15919833
2022 Insights into the Role of Gremlin-1, a Bone Morphogenic Protein Antagonist, in Cancer Initiation and Progression. Biomedicines 17 35203511
2020 Vital Roles of Gremlin-1 in Pulmonary Arterial Hypertension Induced by Systemic-to-Pulmonary Shunts. Journal of the American Heart Association 17 32750294
2019 GREM1 overexpression inhibits proliferation, migration and angiogenesis of osteosarcoma. Experimental cell research 17 31525341
2023 GREM1 signaling in cancer: tumor promotor and suppressor? Journal of cell communication and signaling 16 37615860
2022 Role of gremlin-1 in the pathophysiology of the adipose tissues. Cytokine & growth factor reviews 16 36155165
2020 Gremlin 1 depletion in vivo causes severe enteropathy and bone marrow failure. The Journal of pathology 16 32297672
2020 Role of miR-218-GREM1 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma: An in vivo and vitro study based on microarray data. Journal of cellular and molecular medicine 16 33107676
2022 Gremlin aggravates periodontitis via activation of the nuclear factor-kappa B signaling pathway. Journal of periodontology 15 34993960
2020 Pancreatic stromal Gremlin 1 expression during pancreatic tumorigenesis. Genes & diseases 15 35005111
2016 Platelets as a novel source of Gremlin-1: Implications for thromboinflammation. Thrombosis and haemostasis 15 27929199
2015 GREM1 germline mutation screening in Ashkenazi Jewish patients with familial colorectal cancer. Genetics research 15 25992589
2008 Expression of gremlin, a bone morphogenetic protein antagonist,is associated with vascular calcification in uraemia. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 14 19028757
2023 TAF15 regulates the BRD4/GREM1 axis and activates the gremlin-1-NF-κB pathway to promote OA progression. Regenerative therapy 13 37496731

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