Affinage

LGR6

Leucine-rich repeat-containing G-protein coupled receptor 6 · UniProt Q9HBX8

Length
967 aa
Mass
104.3 kDa
Annotated
2026-04-28
71 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LGR6 is a leucine-rich repeat-containing G protein-coupled receptor that functions as a stem/progenitor cell marker and signaling hub across multiple tissues, integrating R-spondin–dependent Wnt/β-catenin potentiation with maresin 1 (MaR1)–dependent pro-resolving signaling. LGR6 binds R-spondins 1–3 with high affinity to enhance Wnt/β-catenin signaling via LRP6 phosphorylation and β-catenin stabilization—without coupling to heterotrimeric G proteins or β-arrestin—while MaR1 binding activates cAMP/CREB signaling, establishing two distinct ligand-dependent signaling modes through a single receptor (PMID:22615920, PMID:34856421, PMID:31657786). Lgr6 marks self-renewing stem/progenitor populations in skin epidermis, hair follicle, taste buds, nail, mammary gland, lung mesenchyme, and bone, where it is functionally required for tissue homeostasis, wound repair, and regeneration; Lgr6 loss impairs wound healing, fracture repair, osteogenesis, and digit tip regeneration, and predisposes to squamous cell carcinoma (PMID:20223988, PMID:26460010, PMID:28945253, PMID:36708855). MaR1–LGR6 signaling drives pro-resolving immune functions including macrophage efferocytosis, Treg-mediated suppression of type 2 inflammation, attenuation of vascular remodeling, and anti-neuroinflammatory microglial polarization, while a human frameshift variant in LGR6 reduces neutrophil phagocytosis and alters innate immune responses (PMID:31657786, PMID:36595677, PMID:34320253, PMID:38718314).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 Medium

    Identification of LGR6 as a distinct subfamily member of leucine-rich repeat GPCRs established its structural class but left its ligand and signaling mode unknown.

    Evidence Phylogenetic and sequence analysis with mutagenesis of related LGR7; LGR6 signaling inferred by homology

    PMID:10935549

    Open questions at the time
    • LGR6 signaling inferred from LGR7 rather than directly tested
    • no endogenous ligand identified
    • no functional role assigned
  2. 2010 High

    The demonstration that Lgr6 marks the most primitive epidermal stem cells capable of generating all skin lineages established LGR6 as a bona fide stem cell marker, shifting the field from receptor characterization to stem cell biology.

    Evidence Knock-in reporter alleles with genetic lineage tracing, cell ablation, and wound healing in mice

    PMID:20223988

    Open questions at the time
    • ligand for LGR6 still unknown
    • mechanism by which LGR6 maintains stemness undefined
    • unclear whether LGR6 is functionally required or merely a marker
  3. 2012 High

    Identification of R-spondins 1–3 as high-affinity LGR6 ligands that potentiate Wnt/β-catenin signaling via LRP6 phosphorylation—without G protein or β-arrestin coupling—defined LGR6's molecular signaling mechanism and distinguished it from classical GPCR activation.

    Evidence Direct binding affinity assays, LRP6 phosphorylation, G protein/β-arrestin coupling assays, cancer mutant loss-of-function analysis

    PMID:22615920

    Open questions at the time
    • whether additional non-R-spondin ligands exist was unknown
    • structural basis of R-spondin binding unresolved
    • in vivo consequence of R-spondin–LGR6 interaction not demonstrated
  4. 2014 High

    Extending LGR6's stem cell role beyond skin, the finding that Lgr6+ cells generate taste bud organoids and contribute to taste papillae in vivo established LGR6 as a pan-tissue stem/progenitor marker, while nerve-dependence of Lgr6 expression revealed niche-dependent regulation.

    Evidence Single-cell organoid culture from Lgr6+ taste cells with lineage tracing; nerve ablation with Lgr6 expression analysis in skin

    PMID:24499442 PMID:25368147

    Open questions at the time
    • whether LGR6 is functionally required in taste or merely marks progenitors
    • molecular mediator of nerve-to-Lgr6 signaling unknown
  5. 2015 High

    Demonstration that Lgr6 knockout mice have impaired nail and digit tip regeneration, and that Lgr6+ skin progenitors undergo neutral competition, established LGR6 as functionally required for regeneration rather than merely a passive marker.

    Evidence Lgr6 knockout mouse phenotyping with microCT; multicolor Confetti lineage tracing with quantitative clonal analysis

    PMID:26460010 PMID:26607954

    Open questions at the time
    • downstream signaling pathway mediating regeneration unresolved
    • whether Wnt potentiation is the operative mechanism in regeneration untested
  6. 2016 High

    Lgr6+ mammary progenitors were shown to be unipotent yet capable of tumor initiation upon oncogenic mutation, linking LGR6-marked cells to cancer biology and demonstrating that depletion of Lgr6+ cells impairs tumor growth.

    Evidence Genetic lineage tracing with conditional oncogene activation and diphtheria toxin-mediated cell depletion in MMTV-PyMT model

    PMID:27798604

    Open questions at the time
    • whether LGR6 signaling itself drives tumor initiation or merely marks the cell of origin
    • applicability to human breast cancer undetermined
  7. 2017 High

    Three advances refined LGR6 biology: Lgr6+ lung mesenchymal cells were shown to promote airway repair via Wnt-Fgf10 cooperation; Lgr6 knockout predisposed to squamous cell carcinoma with compensatory Lgr5 upregulation; and monoclonal antibodies confirmed R-spondin 1 binding to the LGR6 ectodomain.

    Evidence scRNA-seq and organoid co-culture with genetic ablation in lung; germline Lgr6 knockout with skin carcinogenesis; competitive mAb binding assays

    PMID:28013222 PMID:28886383 PMID:28945253

    Open questions at the time
    • LGR5/LGR6 functional redundancy mechanisms unclear
    • structural detail of R-spondin–ectodomain interaction lacking
    • whether Lgr6+ lung cells are stem cells or niche support cells debated
  8. 2019 High

    Discovery of maresin 1 (MaR1) as a second, structurally distinct LGR6 ligand that activates phagocyte functions via ERK/CREB phosphorylation revealed LGR6 as a dual-ligand receptor bridging Wnt potentiation and pro-resolving lipid mediator biology.

    Evidence Unbiased GPCR screen of >200 receptors, radiolabeled 3H-MaR1 binding, LGR6 overexpression/siRNA with phagocytosis and efferocytosis assays

    PMID:31657786

    Open questions at the time
    • structural basis for dual ligand recognition unknown
    • whether MaR1 and R-spondin compete for the same binding site unresolved
    • downstream G protein coupling for MaR1 signaling not fully characterized
  9. 2021 High

    The dual signaling modes of LGR6 were formally dissected: RSPO2 activates Wnt/β-catenin while MaR1 activates cAMP, and Lgr6 knockout mice show reduced trabecular bone mass, establishing pathway-specific ligand outputs and an in vivo osteogenic requirement.

    Evidence CRISPR Lgr6 knockout mice with microCT and MSC osteodifferentiation; parallel Wnt and cAMP pathway assays with RSPO2 vs MaR1

    PMID:34856421

    Open questions at the time
    • signaling intermediates coupling LGR6 to cAMP production unidentified
    • whether both pathways operate simultaneously in vivo unclear
  10. 2021 High

    MaR1–LGR6 signaling was placed upstream of macrophage efferocytosis and TGF-β2 in vascular protection, while in epidermis intravital imaging confirmed nerve-dependent Lgr6 stem cell wound repair with compensatory hair follicle stem cell recruitment, and a Wnt/β-catenin–TCF7L2 positive feedback loop was identified in cervical cancer stem cells.

    Evidence AAA model with SMC-TGFβr2 knockout epistasis; intravital two-photon imaging with cell ablation and scRNA-seq; TOP/FOP reporter with ChIP at LGR6 promoter

    PMID:34102139 PMID:34320253 PMID:34489551

    Open questions at the time
    • TGF-β2 induction mechanism downstream of LGR6 undefined
    • whether TCF7L2 feedback loop operates in normal tissue or only cancer stem cells unknown
  11. 2023 High

    Multiple studies expanded LGR6's immune and skeletal roles: MaR1–LGR6 on Tregs resolves RSV-induced lung inflammation; MaR1–LGR6–CREB/JMJD3/IRF4 attenuates neuroinflammation; Lgr6-null osteoprogenitors show impaired fracture healing via attenuated Wnt signaling; and LGR6 is regulated by ZNRF3-mediated proteasomal degradation in myoblasts.

    Evidence Lgr6 knockout mice with RSV infection and immune profiling; SAH rat model with pathway inhibitors; Lgr6-null fracture model with microCT; C2C12 siRNA/overexpression with ZNRF3 knockdown

    PMID:36595677 PMID:36708855 PMID:37240382 PMID:38340785

    Open questions at the time
    • ZNRF3-LGR6 ubiquitination sites and regulation not mapped
    • whether JMJD3/IRF4 pathway is specific to microglia or generalizable unknown
    • BMP–Wnt crosstalk through LGR6 only partially characterized
  12. 2024 High

    Cardiac and vascular studies revealed LGR6 as a cardioprotective receptor: RSPO3–LGR6 activates STAT3/PGC1α to prevent ferroptosis in diabetic cardiomyopathy, suppresses STAT2/ZBP1-mediated necroptosis after I/R injury, and MaR1–LGR6 signals via CaMKII/Nrf2/HO-1 to attenuate hypertensive vascular remodeling; a human LGR6 frameshift variant linked receptor loss to impaired neutrophil phagocytosis and altered innate immunity.

    Evidence Cardiac-specific LGR6 KO/overexpression with RSPO3 rescue in diabetes and I/R models; LGR6 KO hypertension model; human variant analysis with functional immune assays in UK Biobank

    PMID:38463394 PMID:38718314 PMID:39038735 PMID:39471639

    Open questions at the time
    • structural basis for RSPO3 vs MaR1 pathway divergence at LGR6 unresolved
    • human genetic confirmation of cardiac phenotypes lacking
    • whether LGR6 frameshift variant affects Wnt signaling in human immune cells untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for dual ligand recognition (R-spondins vs MaR1), whether both ligand systems operate in the same cell simultaneously, the complete signaling intermediates linking LGR6 to cAMP production, and the extent of functional redundancy with LGR4 and LGR5 across tissues.
  • no crystal/cryo-EM structure of LGR6 with either ligand
  • G protein coupling mechanism for MaR1 signaling undefined
  • systematic comparison of LGR4/5/6 functional redundancy across tissues lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 2
Partners
CTNNB1HNRNPKLRP6RSPO1RSPO2RSPO3TCF7L2ZNRF3

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 LGR6 was identified as a leucine-rich repeat-containing G protein-coupled receptor with a subgroup-specific hinge region after leucine-rich repeats, belonging to a subfamily (LGR4-6) distinct from glycoprotein hormone receptors and LGR7. LGR6 is not coupled to heterotrimeric G proteins following ligand stimulation (established by analogy with LGR7 mutagenesis studies). Phylogenetic analysis, sequence analysis, single amino acid mutagenesis of conserved residues to produce constitutively active receptors, signaling pathway analysis (PKA vs PLC) Molecular endocrinology Medium 10935549
2010 Lgr6 marks the most primitive epidermal stem cells residing in a region directly above the follicle bulge. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland, and interfollicular epidermis; postnatal Lgr6+ cells generate sebaceous gland and interfollicular epidermis; adult Lgr6+ cells execute long-term wound repair including formation of new hair follicles. Knock-in reporter alleles (Lgr6-EGFP-IRES-CreERT2), genetic lineage tracing in mice, cell ablation, wound healing assays Science High 20223988
2012 LGR6 binds R-spondins 1-3 with high affinity and responds to R-spondin stimulation to enhance Wnt/β-catenin signaling through increased LRP6 phosphorylation. LGR6 is not coupled to heterotrimeric G proteins or β-arrestin following R-spondin stimulation. A somatic colon cancer mutant of LGR6 fails to bind and respond to R-spondin (loss-of-function). Overexpression of wild-type LGR6 in HeLa cells leads to increased cell migration following co-treatment with R-spondin1 and Wnt3a. Binding affinity assays, LRP6 phosphorylation assays, G protein coupling assays, β-arrestin recruitment assays, functional analysis of cancer-associated mutants, cell migration assays PloS one High 22615920
2014 Lgr6 expression in skin epidermis is controlled by nerve endings and Schwann cells; ablation of cutaneous nerves leads to degeneration of Schwann cells and diminished expression of Lgr6, demonstrating niche-dependent regulation of Lgr6 expression. Immunofluorescence localization, nerve ablation experiments, analysis of Lgr6 expression changes post-denervation in mouse skin Experimental dermatology Medium 24499442
2014 Single isolated Lgr6+ taste cells can generate continuously expanding 3D organoids containing mature taste receptor cells; genetic lineage tracing showed Lgr6+ cells give rise to taste bud cells in taste papillae in both anterior and posterior tongue, demonstrating Lgr6 marks taste stem/progenitor cells. Single-cell organoid culture, calcium imaging assays, genetic lineage tracing (Lgr6-EGFP-CreERT2), RT-PCR Proceedings of the National Academy of Sciences High 25368147
2015 Lgr6 is expressed in nail matrix epithelium and marks nail stem cells; genetic lineage analysis shows Lgr6+ cells give rise to the nail during homeostatic growth and contribute to the blastema during digit tip regeneration. Lgr6-deficient mice exhibit nail and bone regeneration defects, establishing a direct functional role in digit tip regeneration. Genetic lineage tracing (Lgr6-EGFP-CreERT2/Rosa26 reporter), Lgr6 knockout mouse analysis, histology, microCT Proceedings of the National Academy of Sciences High 26460010
2015 Lgr6+ cells in skin (IFE, isthmus, SG) constitute long-term self-renewing populations; quantitative clonal dynamics analysis revealed Lgr6+ progenitor cells compete neutrally in the IFE, isthmus, and SG, indicating population asymmetry as the underlying mode of tissue renewal. Multicolor lineage tracing (Confetti reporter), quantitative clonal analysis, transcriptional profiling of sorted Lgr6+ cells Stem cell reports High 26607954
2016 Lgr6 marks rare mammary gland progenitor cells that are unipotent, expand clonally during puberty, regain proliferative potency during pregnancy, and can initiate luminal mammary tumors upon oncogenic mutation. Depletion of Lgr6+ cells in the MMTV-PyMT model significantly impaired tumor growth. Genetic lineage tracing, conditional oncogenic mutation in Lgr6+ cells, diphtheria toxin-mediated cell depletion, tumor growth analysis Nature cell biology High 27798604
2017 Lgr6+ cells in the adult lung comprise a subpopulation of smooth muscle cells surrounding airway epithelia. Lgr6+ mesenchymal cells promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6+ cells impairs airway injury repair in vivo. Genetic lineage tracing, single-cell RNA sequencing, organoid co-culture, genetic ablation (diphtheria toxin), airway injury model Cell High 28886383
2017 Lgr6 downregulation in vivo causes increased epidermal proliferation with expanded lineage tracing from epidermal stem cells. Germline knockout of Lgr6 predisposes mice to squamous cell carcinoma development through a mechanism including compensatory upregulation of Lgr5. Lgr6-EGFP-CreERT2/Rosa26-Tomato reporter lineage tracing, germline Lgr6 knockout, single-molecule in situ hybridization, FACS sorting, skin carcinogenesis model Nature genetics High 28945253
2019 Maresin 1 (MaR1) is a stereoselective activator of human LGR6. MaR1 specifically binds LGR6 (confirmed with 3H-labeled MaR1) and activates it in phagocytes to enhance phagocytosis, efferocytosis, and phosphorylation of ERK and CREB. MaR1 actions were amplified by LGR6 overexpression and diminished by LGR6 gene silencing. Unbiased GPCR screening (>200 GPCRs), reporter cells expressing LGR6, functional impedance sensing, radiolabeled ligand binding (3H-MaR1), LGR6 overexpression and siRNA knockdown in phagocytes, phagocytosis/efferocytosis assays, phosphoprotein analysis Journal of Clinical Investigation High 31657786
2019 LGR6 promotes Wnt/β-catenin signaling in osteoblastic progenitors by stabilizing β-catenin; LGR6 overexpression promotes osteogenic differentiation and mineralization while LGR6 knockdown inhibits these processes via β-catenin degradation. Lentiviral LGR6 overexpression and knockdown in MC3T3-E1 preosteoblastic cells, β-catenin stability assays, osteogenic differentiation assays, mineralization assays Biochemical and biophysical research communications Medium 31500806
2021 LGR6 marks epidermal stem cells that specialize in wound re-epithelialization; diphtheria toxin-mediated ablation of Lgr6 stem cells delays wound healing. Nerve denervation phenocopies Lgr6 stem cell ablation. Intravital imaging showed wound re-epithelialization by Lgr6 stem cells is diminished following loss of nerves, inducing recruitment of hair follicle stem cells as compensatory response. Loss of niche (nerve) shifts Lgr6 stem cell fate toward differentiation. Diphtheria toxin ablation, skin denervation, intravital two-photon microscopy, single-cell lineage tracing, single-cell RNA sequencing Cell stem cell High 34102139
2021 RSPO2 stimulates LGR6-mediated WNT/β-catenin signaling whereas MaR1 stimulates LGR6-mediated cAMP activity, demonstrating two distinct ligand-dependent signaling functions for LGR6. Lgr6 knockout mice have less trabecular bone mass and reduced ex vivo osteodifferentiation of primary MSCs, establishing that Lgr6 is necessary for normal osteogenesis. In vitro LGR6 knockdown and overexpression in murine osteoblastic cells, CRISPR-Cas9 Lgr6 knockout mice, microCT bone analysis, ex vivo MSC osteodifferentiation, cAMP signaling assays, WNT/β-catenin signaling assays with RSPO2 and MaR1 Bone High 34856421
2021 MaR1 activates LGR6 receptors to upregulate macrophage-dependent efferocytosis, increase TGF-β2 expression, decrease MMP2 activity, and attenuate abdominal aortic aneurysm formation. In vivo inhibition of LGR6 receptors obliterated MaR1-dependent protection. SMC-specific TGFβ receptor knockout abolished MaR1/LGR6 protection, placing TGF-β2 downstream of MaR1-LGR6 signaling. In vivo LGR6 receptor inhibition, AAA mouse model, SMC-TGFβr2 knockout mice, macrophage efferocytosis assays, in vitro MaR1-LGR6 crosstalk studies, MMP2 activity assays FASEB journal High 34320253
2021 LGR6 activates the Wnt/β-catenin signaling pathway in cervical cancer stem cells and forms a positive feedback loop: LGR6 activates Wnt/β-catenin → upregulates TCF7L2 → TCF7L2/β-catenin complex binds LGR6 promoter → enhances LGR6 transcription. RNA sequencing, TOP/FOP luciferase reporter assays, RT-PCR, western blotting, ChIP or promoter binding assays for TCF7L2/β-catenin at LGR6 promoter, FACS sorting of LGR6high cells, functional stemness assays Oncogene Medium 34489551
2022 Mechanical tension preferentially activates and drives differentiation of Lgr6+ epidermal stem cells to promote skin growth, driven in part by the Hippo pathway. Controlled tissue expansion in mice, machine learning-guided 3D tissue reconstruction, single-cell RNA sequencing, Lgr6 lineage tracing Science advances Medium 35476447
2022 MaR1/LGR6 signaling mitigates CXCL1 secretion by epithelial cells in the context of lung ischemia-reperfusion injury, placing LGR6 in a specific cell-type and molecular pathway for resolution of inflammation. LGR6 siRNA knockdown in mice, murine orthotopic lung transplant model, in vitro type II epithelial cell activation studies, cytokine measurement Journal of heart and lung transplantation Medium 36628837
2023 The lncRNA LITTIP binds to LGR6 mRNA and the RNA-binding protein HnRNPK to form a LITTIP/Lgr6/HnRNPK complex; LITTIP promotes LGR6 expression via HnRNPK, and this complex regulates cementogenesis via Wnt/β-catenin signaling. ChIRP (chromatin isolation by RNA purification), RIP (RNA immunoprecipitation), co-transfection experiments, RNA microarray, in vivo PTH administration, Wnt pathway assays International journal of oral science Medium 37558690
2023 Lgr6 is expressed in osteoprogenitors in response to fracture injury; Lgr6-null mice have reduced colony-forming potential, reduced osteogenic differentiation due to attenuated canonical Wnt signaling, lower proportion of self-renewing stem cells, and impaired endochondral ossification and mineralization during fracture healing. Lgr6-null mouse model, colony-forming assays, osteogenic differentiation, Wnt signaling assays, fracture healing model with ALP activity, microCT, histology Bone High 36708855
2023 LGR6 expression is enhanced during BMP-mediated osteogenesis; Lgr6 loss results in downregulation of BMP signaling elements including pSMAD and BMP-associated gene ontology pathways, revealing a molecular interdependency between BMP signaling and Lgr6 in osteogenesis. Lgr6 knockout cells and mice, RNA sequencing, bioinformatic analysis of published single-cell data, biochemical pSMAD assays, gene ontology pathway analysis Bone Medium 39033993
2024 LGR6 deficiency in cardiomyocytes aggravates ferroptosis and disrupted mitochondrial biogenesis in diabetic cardiomyopathy by regulating STAT3/PGC1α signaling; cardiomyocyte-specific LGR6 overexpression ameliorates cardiac dysfunction. LGR6 activation by recombinant RSPO3 treatment also ameliorated cardiac dysfunction and mitochondrial dysfunction. LGR6 knockout mice, AAV9-mediated cardiomyocyte-specific LGR6 overexpression, streptozotocin/high-fat diet diabetes model, RNA sequencing, ChIP assay, STAT3 inhibition, PGC1α activation experiments Metabolism: clinical and experimental High 39038735
2024 RSPO3-LGR6 axis activates Wnt signaling to downregulate STAT2 and ZBP1 expression, thereby inhibiting cardiomyocyte necroptosis after ischemia-reperfusion injury. LGR6 deficiency promoted necroptosis while LGR6 overexpression inhibited it; RSPO3 treatment protected from acute myocardial I/R injury. LGR6 knockout mice, coronary artery ligation I/R model, RNA sequencing, ChIP assays, STAT2 and ZBP1 inhibition experiments, RSPO3 treatment Redox biology High 39471639
2024 MaR1 regulates hypertensive vascular remodeling through LGR6 via a Ca2+/calmodulin-dependent protein kinase II/Nrf2/HO-1 signaling pathway; LGR6 knockout aggravated pathological vascular remodeling that could not be reversed by MaR1 treatment. LGR6 knockout mice, angiotensin II-infused hypertension model, VSMC functional assays (proliferation, migration, phenotype switching, pyroptosis), CaMKII/Nrf2/HO-1 pathway analysis MedComm Medium 38463394
2024 A frameshift variant in LGR6 leads to downregulation of LGR6 expression selectively in neutrophils, monocytes, and NK cells (but not macrophages or CD8+ T cells), linking LGR6 expression to decreased bacterial phagocytosis, increased neutrophil chemotaxis, increased leukotriene B4 production, and altered antiviral responses via TLR3/7/8/9 pathways. Human genetic variant analysis, flow cytometry for LGR6 expression on leukocyte subsets, phagocytosis assays, chemotaxis assays, leukotriene B4 measurement, TLR agonist stimulation, UK Biobank population analysis Blood High 38718314
2017 Monoclonal antibodies against the N-terminal extracellular domain of human LGR6 competitively block R-spondin 1 binding to LGR6, confirming that R-spondin 1 binds to the large ectodomain of LGR6. DNA immunization, whole-cell immunization, flow cytometry screening of hybridomas, competitive binding assays with mAbs and R-spondin 1 Journal of biochemistry Medium 28013222
2023 LGR6 activates MaR1-LGR6-CREB/JMJD3/IRF4 signaling pathway to attenuate neuroinflammation after subarachnoid hemorrhage; LGR6 knockdown, CREB inhibition, or JMJD3 inhibition abolished MaR1's anti-neuroinflammatory effects on microglial activation and cytokine expression. SAH rat model, intranasal MaR1 administration, LGR6 siRNA knockdown, KG-501 (CREB inhibitor), GSK-J4 (JMJD3 inhibitor), neurobehavioral testing, histology, biochemical cytokine analysis, microglial activation assessment Neuroscience Medium 38340785
2023 MaR1 alleviates RSV-induced lung inflammation via LGR6 expressed constitutively on Tregs; Lgr6-deficient mice had exacerbated type 2 immune responses, increased viral burden, and blunted responses to MaR1, establishing a MaR1-LGR6 axis that improves Treg suppressive function and upregulates host antiviral genes. Lgr6 knockout mice, RSV infection model, flow cytometry, IL-13 measurement, amphiregulin measurement, interferon-β measurement, RSV viral transcript quantification Proceedings of the National Academy of Sciences High 36595677
2023 LGR6 promotes myoblast differentiation and fusion; Lgr6 mRNA is transiently expressed during myogenic differentiation in response to ATRA (requiring RARα and RARγ agonism). LGR6 loss decreased differentiation and fusion indices; LGR6 expression is downregulated by the ubiquitin-proteasome system involving ZNRF3. LGR6 augments Wnt/β-catenin signaling activity induced by Wnt3a and R-spondin 2 in myoblasts. C2C12 myoblast differentiation assay, siRNA knockdown of LGR6, exogenous LGR6 expression, ATRA/RAR agonist treatment, proteasome inhibitor treatment, Znrf3 knockdown, Wnt/β-catenin luciferase reporter assay International journal of molecular sciences Medium 37240382

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science (New York, N.Y.) 627 20223988
2000 The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Molecular endocrinology (Baltimore, Md.) 302 10935549
2017 Anatomically and Functionally Distinct Lung Mesenchymal Populations Marked by Lgr5 and Lgr6. Cell 300 28886383
2019 Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions. The Journal of clinical investigation 188 31657786
2014 Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo. Proceedings of the National Academy of Sciences of the United States of America 172 25368147
2011 Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer. Oncogene 106 22002312
2012 LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. PloS one 104 22615920
2015 Lgr6 marks nail stem cells and is required for digit tip regeneration. Proceedings of the National Academy of Sciences of the United States of America 95 26460010
2015 Dynamics of Lgr6⁺ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis. Stem cell reports 88 26607954
2021 Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization. Cell stem cell 75 34102139
2016 Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours. Nature cell biology 72 27798604
2017 Lgr6 is a stem cell marker in mouse skin squamous cell carcinoma. Nature genetics 50 28945253
2016 miR-17-92/p38α Dysregulation Enhances Wnt Signaling and Selects Lgr6+ Cancer Stem-like Cells during Lung Adenocarcinoma Progression. Cancer research 49 27197183
2019 Silencing LGR6 Attenuates Stemness and Chemoresistance via Inhibiting Wnt/β-Catenin Signaling in Ovarian Cancer. Molecular therapy oncolytics 48 31193124
2013 Stimulation of the follicular bulge LGR5+ and LGR6+ stem cells with the gut-derived human alpha defensin 5 results in decreased bacterial presence, enhanced wound healing, and hair growth from tissues devoid of adnexal structures. Plastic and reconstructive surgery 40 24165598
2018 Characterization of Lgr6+ Cells as an Enriched Population of Hair Cell Progenitors Compared to Lgr5+ Cells for Hair Cell Generation in the Neonatal Mouse Cochlea. Frontiers in molecular neuroscience 39 29867341
2023 The Maresin 1-LGR6 axis decreases respiratory syncytial virus-induced lung inflammation. Proceedings of the National Academy of Sciences of the United States of America 37 36595677
2020 Maresin-1 resolution with RORα and LGR6. Progress in lipid research 36 32360520
2014 Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes. Plastic and reconstructive surgery 36 24572851
2014 Epidermal expression of Lgr6 is dependent on nerve endings and Schwann cells. Experimental dermatology 35 24499442
2021 Maresin 1 activates LGR6 signaling to inhibit smooth muscle cell activation and attenuate murine abdominal aortic aneurysm formation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 34 34320253
2022 Mechanical tension mobilizes Lgr6+ epidermal stem cells to drive skin growth. Science advances 32 35476447
2019 LGR6 promotes osteogenesis by activating the Wnt/β-catenin signaling pathway. Biochemical and biophysical research communications 32 31500806
2017 LGR5 and LGR6 in stem cell biology and ovarian cancer. Oncotarget 31 29416699
2022 Resolution of post-lung transplant ischemia-reperfusion injury is modulated via Resolvin D1-FPR2 and Maresin 1-LGR6 signaling. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 30 36628837
2021 LGR6 activates the Wnt/β-catenin signaling pathway and forms a β-catenin/TCF7L2/LGR6 feedback loop in LGR6high cervical cancer stem cells. Oncogene 30 34489551
2024 Cardiomyocyte LGR6 alleviates ferroptosis in diabetic cardiomyopathy via regulating mitochondrial biogenesis. Metabolism: clinical and experimental 29 39038735
2015 Dynamic expression of Lgr6 in the developing and mature mouse cochlea. Frontiers in cellular neuroscience 27 26029045
2018 LGR6 promotes the progression of gastric cancer through PI3K/AKT/mTOR pathway. OncoTargets and therapy 26 29872314
2016 Transplantation of an LGR6+ Epithelial Stem Cell-Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects: The In Vitro Development of Polarized Hair-Bearing Skin. Plastic and reconstructive surgery 26 26818284
2022 Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway. Oxidative medicine and cellular longevity 24 35498124
2021 Mouse LGR6 regulates osteogenesis in vitro and in vivo through differential ligand use. Bone 23 34856421
2012 LGR4 and LGR6 are differentially expressed and of putative tumor biological significance in gastric carcinoma. Virchows Archiv : an international journal of pathology 23 22855134
2022 Maresin-1 and its receptors RORα/LGR6 as potential therapeutic target for respiratory diseases. Pharmacological research 22 35781060
2020 LGR6 Promotes Tumor Proliferation and Metastasis through Wnt/β-Catenin Signaling in Triple-Negative Breast Cancer. Molecular therapy oncolytics 18 32775619
2018 Down-regulation of LGR6 promotes bone fracture recovery using bone marrow stromal cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 29625528
2011 Isolation and in vitro expansion of Lgr6-positive multipotent hair follicle stem cells. Cell and tissue research 17 21484413
2011 Expression patterns of lgr4 and lgr6 during zebrafish development. Gene expression patterns : GEP 17 21570488
2024 LGR6 protects against myocardial ischemia-reperfusion injury via suppressing necroptosis. Redox biology 16 39471639
2024 Maresin-1 ameliorates hypertensive vascular remodeling through its receptor LGR6. MedComm 15 38463394
2023 Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing. Bone 15 36708855
2018 Downregulation of Lgr6 inhibits proliferation and invasion and increases apoptosis in human colorectal cancer. International journal of molecular medicine 14 29693156
2018 Evidence for Lgr6 as a Novel Marker of Osteoblastic Progenitors in Mice. JBMR plus 14 30828690
2021 Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases. Cells 13 34943945
2025 LGR6 modulates intervertebral disc degeneration through regulation of macrophage efferocytosis. Journal of translational medicine 10 40281518
2023 LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling. International journal of oral science 9 37558690
2022 LGR6 Acts as an Oncogene and Induces Proliferation and Migration of Gastric Cancer Cells. Critical reviews in eukaryotic gene expression 9 35695661
2021 LGR6 promotes glioblastoma malignancy and chemoresistance by activating the Akt signaling pathway. Experimental and therapeutic medicine 9 34659510
2020 WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer. Anticancer research 9 33109540
2024 An LGR6 frameshift variant abrogates receptor expression on select leukocyte subsets and is associated with viral infections. Blood 7 38718314
2020 Canine Epithelial Skin Tumours: Expression of the Stem Cell Markers Lgr5, Lgr6 and Sox9 in Light of New Cancer Stem Cell Theories. Veterinary sciences 7 32397255
2019 Lgr6: From Stemness to Cancer Progression. Journal of lung health and diseases 7 31236545
2023 The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer. Thoracic cancer 6 38014454
2018 G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma. Frontiers of medicine 6 29971639
2025 Maresin 1-LGR6 axis mitigates inflammation and posttraumatic osteoarthritis after transection of the anterior cruciate ligament in mice. Osteoarthritis and cartilage 5 40139646
2024 Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage. Neuroscience 5 38340785
2024 Signaling pathways associated with Lgr6 to regulate osteogenesis. Bone 5 39033993
2023 All-Trans Retinoic Acid-Responsive LGR6 Is Transiently Expressed during Myogenic Differentiation and Is Required for Myoblast Differentiation and Fusion. International journal of molecular sciences 5 37240382
2021 LGR6 marks nephron progenitor cells. Developmental dynamics : an official publication of the American Association of Anatomists 4 33848015
2020 Epithelial stem cell marker LGR6 expression identifies a low-risk subgroup in human papillomavirus positive oropharyngeal squamous cell carcinoma. Oral oncology 4 32244172
2024 Reassessing the genetic lineage tracing of lingual Lgr5 and Lgr6 cells in vivo. Animal cells and systems 3 39040684
2023 DNA methylation and expression of LGR6 gene in ankylosing spondylitis: A case-control study. Human immunology 3 37802707
2023 WNT enhancing signals in pancreatic cancer are transmitted by LGR6. Aging 2 37770230
2022 LGR6-dependent conditional inactivation of E-cadherin and p53 leads to invasive skin and mammary carcinomas in mice. Neoplasia (New York, N.Y.) 2 36371908
2012 Identification and developmental expression of leucine-rich repeat-containing G protein-coupled receptor 6 (lgr6) in the medaka fish, Oryzias latipes. Development genes and evolution 2 22576653
2024 Lgr6-expressing functional nail stem-like cells differentiated from human-induced pluripotent stem cells. PloS one 1 38743670
2017 Generation and characterization of monoclonal antibodies against human LGR6. Journal of biochemistry 1 28013222
2017 RNA-seq analysis of Lgr6+ stem cells and identification of an Lgr6 isoform. Experimental dermatology 1 28987003
2026 Maresin1 mitigates morphine analgesic tolerance via the Lgr6 pathway. Progress in neurobiology 0 41956197
2025 Recombinant human collagen XVII promotes skin repair and regeneration by upregulating Lgr6 signaling pathway. International journal of biological macromolecules 0 41380874
2025 Lgr6+ cells in the biological system during homeostasis and injury. Genes & diseases 0 41938713