Leucine-rich repeat-containing G-protein coupled receptor 6 · UniProt Q9HBX8
LGR6 is a leucine-rich repeat-containing G protein-coupled receptor of the LGR4-6 subgroup that marks and sustains tissue-resident stem and progenitor populations across multiple epithelia while transducing two distinct ligand-dependent signals (PMID:10935549, PMID:20223988, PMID:34856421). As a high-affinity receptor for R-spondins 1-3, binding through its large N-terminal extracellular domain, LGR6 potentiates canonical Wnt/β-catenin signaling by promoting LRP6 phosphorylation and β-catenin stabilization without coupling to heterotrimeric G proteins or β-arrestin (PMID:22615920, PMID:28013222, PMID:31500806). A second ligand, the pro-resolving lipid mediator maresin 1 (MaR1), is a stereoselective LGR6 agonist that drives cAMP-dependent and ERK/CREB signaling in phagocytes to enhance phagocytosis and efferocytosis, establishing LGR6 as a receptor with both Wnt-potentiating and cAMP-coupled outputs (PMID:31657786, PMID:34856421). Through Wnt/β-catenin activation, LGR6 maintains the most primitive epidermal stem cells and drives wound re-epithelialization, nail and digit-tip regeneration, mammary progenitor expansion, lung airway repair, and osteogenic differentiation and fracture healing (PMID:20223988, PMID:26460010, PMID:34102139, PMID:34856421, PMID:36708855, PMID:27798604). The Wnt-potentiating axis also underlies oncogenic roles, where LGR6 supports cancer stem-cell phenotypes and chemoresistance and can engage a TCF7L2-β-catenin positive feedback loop that amplifies its own transcription (PMID:31193124, PMID:34489551, PMID:28945253). Via the MaR1 axis, LGR6 mediates pro-resolving and cytoprotective functions in macrophages, neutrophils, regulatory T cells, and parenchymal cells, attenuating injury in vascular, cardiac, renal, pulmonary, and neuroinflammatory disease models through pathways including cAMP-SOD2, STAT3/PGC1α, and Wnt-dependent suppression of necroptosis (PMID:34320253, PMID:39038735, PMID:39471639, PMID:35498124, PMID:36595677). A human LGR6 frameshift variant downregulates the receptor in neutrophils, monocytes, and NK cells and alters their phagocytic, chemotactic, and TLR-responsive functions, linking LGR6 to innate immune competence (PMID:38718314).
Established LGR6 as a distinct leucine-rich repeat GPCR, defining its receptor architecture before any ligand was known.
Evidence molecular cloning, phylogenetic and structural domain analysis
Resolved whether LGR6 marks a functional stem cell pool by showing Lgr6+ cells are the most primitive epidermal stem cells generating all skin lineages and executing wound repair.
Evidence knock-in reporter alleles with genetic lineage tracing in mouse skin
Identified the first LGR6 ligand and its signaling logic, showing R-spondins bind LGR6 and potentiate Wnt/β-catenin via LRP6 without G protein or β-arrestin coupling.
Evidence binding assays, Wnt luciferase reporter, LRP6 phosphorylation blots, G protein/β-arrestin assays, cancer mutagenesis in cell lines
Extended LGR6 stem/progenitor function beyond skin to mammary gland and linked it to tumorigenesis.
Evidence lineage tracing, cell depletion, oncogenic induction, MMTV-PyMT tumor model; parallel NSCLC miR-17-92/p38α-Wnt study
Localized R-spondin binding to the LGR6 N-terminal ectodomain and defined Lgr6 as a niche-supplying mesenchymal marker in lung repair.
Evidence competitive antibody binding to ectodomain; lung lineage tracing, scRNA-seq, organoids and genetic ablation
PMID:28013222 PMID:28886383 PMID:28945253
Discovered a second, structurally unrelated ligand by identifying MaR1 as a stereoselective LGR6 agonist that drives phagocyte pro-resolving functions, revealing dual ligand recognition.
Evidence unbiased >200 GPCR screen, [3H]-MaR1 radioligand binding, reporter assays, gain/loss-of-function phagocytosis/efferocytosis with ERK/CREB phosphorylation
PMID:31193124 PMID:31500806 PMID:31657786
Formally separated LGR6's two signaling arms, showing RSPO2 drives Wnt/β-catenin while MaR1 drives cAMP from the same receptor, with bone as the in vivo readout.
Evidence CRISPR-Cas9 Lgr6 knockout mice, microCT, osteodifferentiation, Wnt reporter and cAMP assays
Demonstrated MaR1-LGR6 pro-resolving signaling protects multiple tissues, defining cAMP-SOD2 and Treg-mediated antiviral mechanisms.
Evidence in vivo LGR6 siRNA/knockout in diabetic kidney, lung I/R, and RSV models; cAMP/SOD2 and Treg suppressive function assays
PMID:34320253 PMID:35498124 PMID:36595677 PMID:36628837
Connected LGR6 to mitochondrial, cell-death, and vascular protective programs and to human innate immune function via a loss-of-function variant.
Evidence LGR6 KO/OE mice with RNA-seq and ChIP defining STAT3/PGC1α, STAT2/ZBP1/Wnt, and CaMKII/NRF2/HO-1 axes; human frameshift variant with primary-cell phenotyping and UK Biobank data
PMID:38463394 PMID:38718314 PMID:39038735 PMID:39471639
| 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. Unlike LGR7, LGR6 lacks the LDL receptor cysteine-rich motif at the N terminus. Phylogenetic analysis placed LGR6 in the LGR4-6 subgroup, distinct from glycoprotein hormone receptors and LGR7. | Molecular cloning, phylogenetic analysis, structural domain analysis | Molecular endocrinology | Medium | 10935549 |
| 2012 | LGR6 binds R-spondins 1–3 with high affinity and potentiates Wnt/β-catenin signaling through increased LRP6 phosphorylation. LGR6 is not coupled to heterotrimeric G proteins or β-arrestin following R-spondin stimulation. A colon cancer somatic mutation in LGR6 abolishes R-spondin binding and response (loss-of-function), while two other cancer mutations had no significant effect on receptor function. Overexpression of wild-type LGR6 in HeLa cells increases cell migration following co-treatment with R-spondin1 and Wnt3a compared to loss-of-function mutant. | Binding assays, luciferase reporter (Wnt/β-catenin), LRP6 phosphorylation western blot, β-arrestin recruitment assay, G protein coupling assay, cell migration assay, site-directed mutagenesis | PloS one | High | 22615920 |
| 2017 | In the adult lung, Lgr6+ cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia. These 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 culture, genetic cell ablation, in vivo injury model | Cell | High | 28886383 |
| 2019 | Maresin 1 (MaR1) is a stereoselective activator of human LGR6 identified by unbiased screening of >200 GPCRs. MaR1 specifically binds LGR6 (confirmed by [3H]-labeled MaR1 binding). MaR1 activation of LGR6 in phagocytes enhanced phagocytosis, efferocytosis, and phosphorylation of ERK and CREB. These actions were amplified by LGR6 overexpression and diminished by LGR6 gene silencing. | Unbiased GPCR screen (>200 receptors), reporter cell assay, functional impedance sensing, radioligand binding ([3H]-MaR1), LGR6 overexpression and siRNA knockdown, phagocytosis/efferocytosis assays, phosphoprotein analysis | The Journal of clinical investigation | High | 31657786 |
| 2010 | Lgr6 marks the most primitive epidermal stem cell population located in a region directly above the follicle bulge in adult hair follicles, expressing none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland, and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, with contribution to hair lineages diminishing with age. Adult Lgr6+ cells executed long-term wound repair including formation of new hair follicles. | Knock-in allele generation, genetic lineage tracing, histology, immunofluorescence | Science | High | 20223988 |
| 2015 | Lgr6 is expressed within cells of the nail matrix epithelium and in a subset of bone and eccrine sweat gland cells. Genetic lineage tracing demonstrated that Lgr6-expressing cells give rise to the nail during homeostatic growth, establishing Lgr6 as a nail stem cell marker. Lgr6-expressing cells contribute to the blastema during digit tip regeneration. Lgr6-deficient mice exhibit nail and bone regeneration defects. | Genetic lineage tracing, Lgr6-deficient mouse analysis, histology, digit tip amputation/regeneration model | Proceedings of the National Academy of Sciences | High | 26460010 |
| 2021 | Lgr6 marks a regionally restricted population of epidermal stem cells that interact with nerves and specialize in wound re-epithelialization. Diphtheria toxin-mediated ablation of Lgr6+ stem cells delays wound healing. Skin denervation phenocopies this effect, diminishing wound re-epithelialization by Lgr6+ stem cells. Loss of nerve niche shifts fate of Lgr6+ stem cells toward differentiation. | Diphtheria toxin-mediated cell ablation, skin denervation, intravital imaging, single-cell lineage tracing, gene expression analysis | Cell stem cell | High | 34102139 |
| 2019 | Silencing LGR6 in ovarian cancer cells inhibited cancer stem cell-like phenotype and chemoresistance in vitro and improved cisplatin sensitivity in vivo. Mechanistic investigation showed that silencing LGR6 repressed Wnt/β-catenin signaling, as determined by luciferase assays and GSEA. | siRNA knockdown, luciferase reporter assay (Wnt/β-catenin), GSEA, in vitro functional assays, in vivo xenograft | Molecular therapy oncolytics | Medium | 31193124 |
| 2021 | LGR6 promotes osteogenesis in vitro and in vivo. In murine osteoblastic cells, LGR6 overexpression increased β-catenin stability to potentiate Wnt/β-catenin signaling, promoting osteogenic differentiation and mineralization. LGR6 knockdown decreased β-catenin stability and inhibited osteogenesis. CRISPR-Cas9 Lgr6 knockout mice have reduced trabecular bone mass. Mechanistically, RSPO2 stimulates LGR6-mediated Wnt/β-catenin signaling, whereas MaR1 stimulates LGR6-mediated cAMP activity, indicating two ligand-dependent signaling functions. | Lentiviral overexpression/knockdown, CRISPR-Cas9 knockout mice, microCT, ex vivo osteodifferentiation, in vitro signaling assays (Wnt reporter, cAMP assay), western blot | Bone | High | 34856421 |
| 2021 | LGR6 activation by MaR1 attenuated abdominal aortic aneurysm (AAA) growth in mice. In vivo inhibition of LGR6 receptors abolished MaR1-dependent protection. MaR1-LGR6 interaction upregulated TGF-β2 expression and decreased MMP2 activity in macrophage-apoptotic SMC crosstalk in vitro. MaR1 via LGR6 also upregulated macrophage-dependent efferocytosis of apoptotic SMCs. | In vivo LGR6 inhibition, elastase AAA mouse model, smooth muscle cell-specific TGFβr2 knockout mice, in vitro macrophage-SMC co-culture, MMP2 activity assay, efferocytosis assay | FASEB journal | Medium | 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 signaling, which upregulates TCF7L2 expression; TCF7L2 then complexes with β-catenin in the nucleus to enhance LGR6 transcription by binding the LGR6 promoter. | RNA sequencing, TOP/FOP luciferase reporter assay, RT-PCR, western blotting, FACS isolation of LGR6high cells, transcription factor binding assay | Oncogene | Medium | 34489551 |
| 2024 | LGR6 regulates mitochondrial biogenesis and suppresses ferroptosis in diabetic cardiomyopathy via the STAT3/PGC1α signaling pathway. LGR6 knockout aggravated, and cardiomyocyte-specific LGR6 overexpression ameliorated, cardiac dysfunction, ferroptosis, and mitochondrial biogenesis disruption. STAT3 inhibition and PGC1α activation abrogated LGR6 knockout-induced mitochondrial dysfunction. LGR6 activation by recombinant RSPO3 ameliorated cardiac dysfunction, ferroptosis, and mitochondrial dysfunction in diabetic mice. | LGR6 knockout mice, cardiomyocyte-specific AAV9-LGR6 overexpression, RNA sequencing, chromatin immunoprecipitation (ChIP), in vitro high glucose model, RSPO3 treatment | Metabolism | High | 39038735 |
| 2024 | LGR6 protects against myocardial ischemia-reperfusion injury by suppressing necroptosis via the Wnt signaling pathway. LGR6 regulates expression of STAT2 and ZBP1 by activating Wnt signaling, thereby inhibiting cardiomyocyte necroptosis. LGR6 deficiency promoted and overexpression inhibited necroptosis and acute myocardial injury after I/R. RSPO3 activation of LGR6 protected mice from acute myocardial I/R injury. Inhibiting STAT2 and ZBP1 alleviated LGR6 deficiency-induced necroptosis. | LGR6 knockout mice, in vivo I/R model (left anterior descending coronary artery ligation), RNA sequencing, ChIP assay, RSPO3 treatment, in vitro hypoxia-reoxygenation model | Redox biology | High | 39471639 |
| 2022 | MaR1-LGR6 signaling mitigated CXCL1 secretion by epithelial cells in the context of lung ischemia-reperfusion injury. LGR6 siRNA treatment in mice abolished MaR1-dependent protection against lung I/R injury. | LGR6 siRNA in vivo treatment, hilar-ligation lung I/R model, orthotopic lung transplantation model, in vitro alveolar macrophage and type II epithelial cell assays | The Journal of heart and lung transplantation | Medium | 36628837 |
| 2023 | LGR6 is required for proper fracture healing and bone regeneration. Lgr6-null mice showed deficiency in periosteal progenitor proliferation, reduced ALP activity, impaired endochondral ossification, and decreased mineralization during fracture repair. Skeletal progenitors from Lgr6-null mice had reduced colony-forming potential and attenuated canonical Wnt signaling. Lgr6-null mice also comprised a lower proportion of self-renewing stem cells. | Lgr6-null mouse model, fracture healing model, ALP activity assay, colony-forming assay, Wnt signaling analysis, histological analysis | Bone | High | 36708855 |
| 2022 | Mechanical tension preferentially activates and drives differentiation of Lgr6+ epidermal stem cells to achieve skin growth, driven in part by the Hippo pathway. This was established through a controlled tissue expansion system in mice combined with machine learning-guided 3D tissue reconstruction and single-cell RNA sequencing. | Controlled tissue expansion in mice, machine learning-guided 3D tissue reconstruction, single-cell RNA sequencing, lineage tracing | Science advances | Medium | 35476447 |
| 2023 | The lncRNA LITTIP binds to mRNA of LGR6 and to the RNA-binding protein HnRNPK, forming a LITTIP/Lgr6/HnRNPK complex. LITTIP promotes LGR6 expression via HnRNPK, and this elevated LGR6 activates Wnt/β-catenin signaling to negatively regulate cementogenesis. | ChIRP (chromatin isolation by RNA purification), RNA immunoprecipitation (RIP), co-transfection, RNA microarray, western blot | International journal of oral science | Medium | 37558690 |
| 2017 | Two anti-LGR6 monoclonal antibodies (43A6 and 43D10) that recognize the large N-terminal extracellular domain of LGR6 competitively blocked the binding of R-spondin 1, confirming that R-spondin 1 binds to the extracellular domain of LGR6. | Monoclonal antibody generation, competitive binding assay, flow cytometry with LGR4/5/6-transfected cells (specificity), immunoblot | Journal of biochemistry | Medium | 28013222 |
| 2023 | LGR6 expression is transiently induced during myogenic differentiation in a retinoic acid receptor (RARα/RARγ)-dependent manner, requiring ATRA. LGR6 loss decreased myoblast differentiation and fusion indices. LGR6 promotes Wnt/β-catenin signaling induced by Wnt3a and R-spondin 2 in myoblasts. LGR6 expression is downregulated by the ubiquitin-proteasome system involving ZNRF3. | siRNA knockdown, lentiviral overexpression, differentiation/fusion index assays, RAR agonist treatment, proteasome inhibitor treatment, Znrf3 knockdown, Wnt reporter assay | International journal of molecular sciences | Medium | 37240382 |
| 2024 | An LGR6 frameshift variant leads to significant downregulation of LGR6 expression specifically in neutrophils, monocytes, and NK cells but not in monocyte-derived macrophages or CD8+ T cells. Loss of LGR6 in neutrophils and monocytes was linked to decreased phagocytosis of bacteria, increased neutrophil chemotaxis, elevated leukotriene B4 production, and increased activation markers. Neutrophils, NK cells, and CD8+ T cells from variant carriers displayed altered responses to TLR3, TLR7/8, and TLR9 agonists. | Human genetic variant analysis, flow cytometry, phagocytosis assay, chemotaxis assay, leukotriene B4 measurement, TLR agonist stimulation, UK Biobank epidemiological data | Blood | Medium | 38718314 |
| 2022 | Maresin 1 alleviates diabetic kidney disease via LGR6-mediated cAMP-SOD2 antioxidant pathway. LGR6 expression was downregulated in DKD and high-glucose-treated HK-2 cells but upregulated by MaR1. LGR6 siRNA knockdown abrogated MaR1's protective effects against glucotoxicity-induced inflammation. | LGR6 siRNA knockdown, in vivo diabetic mouse model (STZ/high fat diet), HK-2 cell high glucose model, cAMP measurement, SOD2 activity assay, inflammatory marker analysis | Oxidative medicine and cellular longevity | Medium | 35498124 |
| 2024 | Maresin 1 activates LGR6 in microglia to attenuate neuroinflammation after subarachnoid hemorrhage via CREB/JMJD3/IRF4 signaling. Knockdown of LGR6, inhibition of CREB phosphorylation, or inhibition of JMJD3 activity abolished MaR1's anti-neuroinflammatory effects. LGR6 and JMJD3 are co-localized with microglia. | LGR6 siRNA knockdown in rats, SAH model (endovascular perforation), immunohistochemistry, neurobehavioral testing, CREB inhibitor (KG-501), JMJD3 inhibitor (GSK-J4), cytokine analysis | Neuroscience | Medium | 38340785 |
| 2023 | In mice lacking Lgr6, RSV infection caused exacerbated type 2 immune responses with increased viral burden and blunted responses to exogenous MaR1. LGR6 was constitutively expressed on regulatory T cells (Tregs). MaR1-LGR6 signaling improved Tregs' suppressive function and upregulated host antiviral genes. | Lgr6 knockout mice, RSV infection model, flow cytometry, cytokine measurement, viral transcript quantification, MaR1 treatment | Proceedings of the National Academy of Sciences | Medium | 36595677 |
| 2024 | MaR1 reduces blood pressure elevation and alleviates vascular remodeling in angiotensin II-infused mice through LGR6. LGR6 knockout aggravated pathological vascular remodeling and could not be reversed by additional MaR1 treatment. Mechanistically, MaR1 regulates vascular smooth muscle cell activity through LGR6 via Ca2+/calmodulin-dependent protein kinase II/NRF2/HO-1 signaling. | LGR6 knockout mice, angiotensin II infusion model, VSMC culture, western blot, functional VSMC assays (proliferation, migration, phenotype switching, pyroptosis) | MedComm | Medium | 38463394 |
| 2024 | LGR6 overexpression in macrophages enhanced efferocytosis of apoptotic nucleus pulposus cells, increased ECM components (COL2A1), decreased matrix-degrading enzymes (MMP13), and inhibited IL-1β-induced apoptosis by upregulating BCL2 and downregulating cleaved caspase 3 and BAX. LGR6 knockdown impaired these effects. | LGR6 shRNA knockdown and overexpression, macrophage-NPC co-culture, efferocytosis assay, western blot, in vivo mouse IVDD model (disc puncture) | Journal of translational medicine | Medium | 40281518 |
| 2014 | Lgr6 expression in the 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 in skin. | Nerve ablation experiments, immunofluorescence co-localization, histological analysis across hair cycle stages | Experimental dermatology | Medium | 24499442 |
| 2018 | LGR6 knockdown in gastric cancer cells downregulated phosphorylated AKT and mTOR and upregulated proapoptotic proteins Bax and Caspase-3, while decreasing antiapoptotic Bcl2. LGR6 controls gastric cancer cell proliferation, apoptosis, migration, and invasion through the PI3K/AKT/mTOR pathway. | Lentiviral shRNA knockdown, lentiviral overexpression, western blot (pAKT, pmTOR), functional assays (proliferation, apoptosis, migration, invasion) | OncoTargets and therapy | Low | 29872314 |
| 2019 | LGR6 promotes osteogenic differentiation and mineralization in osteoblastic progenitor MC3T3-E1 cells by stabilizing β-catenin to potentiate the Wnt/β-catenin signaling pathway. LGR6 knockdown inhibited osteogenesis by enhancing β-catenin degradation. | Lentiviral overexpression and knockdown, β-catenin stability assay, osteogenic differentiation and mineralization assays, western blot | Biochemical and biophysical research communications | Medium | 31500806 |
| 2016 | Lgr6 marks rare mammary gland progenitor cells. Lgr6+ cells in mammary gland are unipotent progenitors that expand clonally during puberty and regain proliferative potency during pregnancy or following ovarian hormone stimulation. Oncogenic mutations in Lgr6+ cells result in expansion of luminal cells and mammary tumors. Depletion of Lgr6+ cells in the MMTV-PyMT model significantly impaired tumor growth. | Lineage tracing, cell depletion experiments, hormonal stimulation, oncogenic mutation induction, MMTV-PyMT tumor model | Nature cell biology | High | 27798604 |
| 2017 | Lgr6, but not Lgr5, acts as an epithelial stem cell marker in squamous cell carcinomas (SCC). Lgr6 downregulation in vivo causes increased epidermal proliferation with expanded lineage tracing from Lgr6+ epidermal stem cells. Lgr6 germline knockout mice are predisposed to SCC development, through a mechanism that includes compensatory upregulation of Lgr5. | Lineage tracing in reporter mice, Lgr6 germline knockout mice, single-molecule in situ hybridization, cell sorting, SCC mouse model | Nature genetics | High | 28945253 |
| 2016 | High levels of miR-19 family members (from the miR-17-92 cluster) target and downregulate p38α kinase in Lgr6+ NSCLC cells, providing a survival signal mediated by increased Wnt/β-catenin activity. Defective repression of the miR-17-92 cluster is responsible for selection of Lgr6+ NSCLC cells with self-renewal and higher tumorigenic potential. | miR target validation, p38α kinase measurement, Wnt/β-catenin reporter assays, cell sorting, tumor formation assays | Cancer research | Medium | 27197183 |
| 2024 | Lgr6 is expressed in osteoprogenitor cells and is dynamically regulated during BMP-mediated osteogenesis. BMP signaling elements including pSMAD and BMP-related gene ontology pathways are downregulated in the absence of Lgr6, indicating a molecular interdependency between Lgr6 and the BMP pathway. | RNA sequencing, bioinformatic analysis of published single-cell data, biochemical assays, BMP stimulation experiments with Lgr6 KO and WT cells | Bone | Medium | 39033993 |
| 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 | 197 | 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 | 174 | 25368147 |
| 2012 | LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. | PloS one | 107 | 22615920 |
| 2011 | Lgr5 and Lgr6 as markers to study adult stem cell roles in self-renewal and cancer. | Oncogene | 107 | 22002312 |
| 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 | 96 | 26460010 |
| 2015 | Dynamics of Lgr6⁺ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis. | Stem cell reports | 89 | 26607954 |
| 2021 | Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization. | Cell stem cell | 80 | 34102139 |
| 2016 | Lgr6 labels a rare population of mammary gland progenitor cells that are able to originate luminal mammary tumours. | Nature cell biology | 73 | 27798604 |
| 2017 | Lgr6 is a stem cell marker in mouse skin squamous cell carcinoma. | Nature genetics | 53 | 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 |
| 2020 | Maresin-1 resolution with RORα and LGR6. | Progress in lipid research | 40 | 32360520 |
| 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 | 38 | 36595677 |
| 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 | 37 | 34320253 |
| 2014 | Epidermal expression of Lgr6 is dependent on nerve endings and Schwann cells. | Experimental dermatology | 36 | 24499442 |
| 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 |
| 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 | 34 | 36628837 |
| 2022 | Mechanical tension mobilizes Lgr6+ epidermal stem cells to drive skin growth. | Science advances | 33 | 35476447 |
| 2024 | Cardiomyocyte LGR6 alleviates ferroptosis in diabetic cardiomyopathy via regulating mitochondrial biogenesis. | Metabolism: clinical and experimental | 32 | 39038735 |
| 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 |
| 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 |
| 2015 | Dynamic expression of Lgr6 in the developing and mature mouse cochlea. | Frontiers in cellular neuroscience | 27 | 26029045 |
| 2022 | Maresin 1 Alleviates Diabetic Kidney Disease via LGR6-Mediated cAMP-SOD2-ROS Pathway. | Oxidative medicine and cellular longevity | 26 | 35498124 |
| 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 |
| 2021 | Mouse LGR6 regulates osteogenesis in vitro and in vivo through differential ligand use. | Bone | 25 | 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 |
| 2024 | LGR6 protects against myocardial ischemia-reperfusion injury via suppressing necroptosis. | Redox biology | 20 | 39471639 |
| 2020 | LGR6 Promotes Tumor Proliferation and Metastasis through Wnt/β-Catenin Signaling in Triple-Negative Breast Cancer. | Molecular therapy oncolytics | 19 | 32775619 |
| 2024 | Maresin-1 ameliorates hypertensive vascular remodeling through its receptor LGR6. | MedComm | 18 | 38463394 |
| 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 |
| 2023 | Wnt-associated adult stem cell marker Lgr6 is required for osteogenesis and fracture healing. | Bone | 16 | 36708855 |
| 2018 | Downregulation of Lgr6 inhibits proliferation and invasion and increases apoptosis in human colorectal cancer. | International journal of molecular medicine | 15 | 29693156 |
| 2018 | Evidence for Lgr6 as a Novel Marker of Osteoblastic Progenitors in Mice. | JBMR plus | 15 | 30828690 |
| 2021 | Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases. | Cells | 14 | 34943945 |
| 2025 | LGR6 modulates intervertebral disc degeneration through regulation of macrophage efferocytosis. | Journal of translational medicine | 13 | 40281518 |
| 2023 | LITTIP/Lgr6/HnRNPK complex regulates cementogenesis via Wnt signaling. | International journal of oral science | 11 | 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 |
| 2025 | Maresin 1-LGR6 axis mitigates inflammation and posttraumatic osteoarthritis after transection of the anterior cruciate ligament in mice. | Osteoarthritis and cartilage | 7 | 40139646 |
| 2024 | An LGR6 frameshift variant abrogates receptor expression on select leukocyte subsets and is associated with viral infections. | Blood | 7 | 38718314 |
| 2023 | The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer. | Thoracic cancer | 7 | 38014454 |
| 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 |
| 2024 | Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage. | Neuroscience | 6 | 38340785 |
| 2024 | Signaling pathways associated with Lgr6 to regulate osteogenesis. | Bone | 6 | 39033993 |
| 2018 | G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma. | Frontiers of medicine | 6 | 29971639 |
| 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 |
| 2023 | DNA methylation and expression of LGR6 gene in ankylosing spondylitis: A case-control study. | Human immunology | 4 | 37802707 |
| 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 | 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 |
| 2017 | Generation and characterization of monoclonal antibodies against human LGR6. | Journal of biochemistry | 2 | 28013222 |
| 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 | 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 |
| 2026 | Omega-3 DHA as a blank canvas: A molecular approximation to how lipid mediators modulate LGR6 in inflammation resolution. | Protein science : a publication of the Protein Society | 0 | 42159296 |
| 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 |
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