Affinage

RSPO3

R-spondin-3 · UniProt Q9BXY4

Length
272 aa
Mass
30.9 kDa
Annotated
2026-04-28
44 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RSPO3 is a secreted potentiator of Wnt signaling that operates through multiple receptor systems to regulate stem cell self-renewal, tissue homeostasis, and organ morphogenesis across diverse developmental and adult contexts. In canonical Wnt/β-catenin signaling, RSPO3 acts principally through LGR4 (and LGR5) receptors to maintain intestinal crypt stem cells—where it is supplied by PDGFRα+ pericryptal stromal myofibroblasts—and to govern adrenal zona glomerulosa identity, gastric stem cell proliferation, osteoblast-mediated bone formation, hepatic metabolic zonation, and leukemia stem cell self-renewal (PMID:29559533, PMID:27313319, PMID:35767364, PMID:34389713, PMID:32559496, PMID:39854351). RSPO3 also engages non-canonical Wnt pathways: it binds syndecan 4 to activate Wnt/PCP signaling via clathrin-mediated endocytosis during embryonic gastrulation, signals through a WNT/Ca²⁺/NFAT axis to control vascular remodeling, and assembles an LGR4–Gab1–Gαi1/3 complex that activates Erk for neuroprotection (PMID:21397842, PMID:26766444, PMID:37805583). PTPRK-RSPO3 gene fusions drive Wnt-dependent colorectal tumorigenesis by expanding Lgr5+ stem cell compartments, and therapeutic anti-RSPO3 antibodies inhibit tumor growth and promote differentiation in these cancers (PMID:26700806, PMID:27511199).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2011 High

    The first mechanistic role for RSPO3 was established in non-canonical Wnt signaling: RSPO3 binds SDC4 and activates Wnt/PCP signaling via clathrin-mediated endocytosis, resolving how R-spondins engage non-canonical pathways during gastrulation.

    Evidence Co-immunoprecipitation, clathrin inhibition, and epistasis with Fz7/Dvl/JNK in Xenopus embryos

    PMID:21397842

    Open questions at the time
    • Whether SDC4-dependent PCP activation operates in mammalian tissues
    • Structural basis of the RSPO3–SDC4 interaction
    • Relationship between SDC4 and LGR receptor pathways
  2. 2014 Medium

    RSPO3 was placed upstream of an LGR4–IQGAP1 signaling axis in cancer cell proliferation and migration, establishing LGR4 as a functional RSPO3 receptor in a disease-relevant context.

    Evidence shRNA knockdown of RSPO3/LGR4/IQGAP1 with in vitro and in vivo tumor/metastasis assays in lung cancer cells

    PMID:25531322

    Open questions at the time
    • IQGAP1's direct binding mode to the RSPO3–LGR4 complex is undefined
    • Whether IQGAP1 dependency is tissue-specific
  3. 2015 High

    PTPRK-RSPO3 fusions were shown to be oncogenic drivers in colorectal cancer, with anti-RSPO3 antibody treatment shrinking patient-derived xenografts and inducing differentiation of the Lgr5+ stem cell compartment.

    Evidence Anti-RSPO3 antibody treatment of PTPRK-RSPO3 fusion-positive CRC patient-derived xenografts with gene expression and stem cell assays

    PMID:26700806

    Open questions at the time
    • Full spectrum of RSPO3 fusion partners in CRC
    • Whether antibody effects are purely through Wnt suppression or additional mechanisms
  4. 2016 High

    Three independent studies established RSPO3 as a tissue-autonomous niche signal: it controls adrenal zona glomerulosa identity via β-catenin/SHH, drives intestinal tumorigenesis when overexpressed in Lgr5+ cells, and regulates vascular remodeling through a non-canonical WNT/Ca²⁺/NFAT axis in endothelium.

    Evidence Conditional Rspo3 KO in adrenal capsule; conditional Rspo3 transgenic in Lgr5+ intestinal cells with Kras epistasis; inducible endothelial-specific Rspo3 KO with Evi/Wls epistasis and NFAT pharmacological phenocopy

    PMID:26766444 PMID:27313319 PMID:27511199

    Open questions at the time
    • Whether adrenal and vascular roles are LGR4-dependent
    • Identity of endothelial RSPO3 receptor(s)
    • Relative contributions of canonical versus non-canonical pathways in each tissue
  5. 2017 Medium

    RSPO3–LGR4 signaling was shown to modulate ERK/FGF signaling to inhibit osteogenic differentiation, and AXIN1 loss was identified as a mechanism of resistance to Wnt pathway blockade in RSPO3-fusion CRC, defining downstream pathway requirements.

    Evidence shRNA knockdown of RSPO3/LGR4 with ERK inhibitors in human adipose-derived stem cells; whole-exome sequencing and RNAi of AXIN1 in PTPRK-RSPO3 fusion CRC cells

    PMID:28100566 PMID:28220828

    Open questions at the time
    • Whether ERK/FGF suppression operates in vivo bone context
    • Whether other Wnt destruction complex components also confer resistance
  6. 2018 High

    PDGFRα+ pericryptal stromal myofibroblasts were identified as the critical in vivo source of RSPO3 for the intestinal stem cell niche, and RSPO3 was shown to disrupt endothelial barrier function via β-catenin/VE-cadherin junctional disorganization.

    Evidence Cell-type-specific Cre-mediated Rspo3 excision in PDGFRα+ cells with organoid rescue; impedance sensing and immunofluorescence in human endothelial monolayers

    PMID:29559533 PMID:30157748

    Open questions at the time
    • Whether other stromal sources compensate long-term
    • The receptor mediating RSPO3's junctional effects on endothelium
  7. 2020 High

    RSPO3's roles expanded to leukemia stem cell maintenance via LGR4, hepatic cholesterol metabolism via LGR4–AMPKα–SREBP2, and depot-specific adipose tissue distribution through differential Wnt activation, revealing metabolic and hematopoietic functions beyond epithelial stem cell niches.

    Evidence Anti-RSPO3 antibody in AML patient-derived xenografts with HOXA9 cooperativity; Lgr4/Rspo3 knockdown mice with AMPKα epistasis; human adipose progenitor assays and zebrafish rspo3 mutant

    PMID:32493999 PMID:32559496 PMID:32926477

    Open questions at the time
    • Whether AML sensitivity is predictable by LGR4 expression alone
    • The direct binding partner mediating AMPKα activation
    • Mechanism of depot-specific differential Wnt signaling
  8. 2021 High

    Osteoblast-derived RSPO3 was established as the principal source of RSPO3 in bone, acting cell-autonomously to regulate vertebral trabecular bone mass and strength through osteoblast proliferation and differentiation.

    Evidence Osteoblast-specific Rspo3 conditional knockout (Runx2-cre) with bone densitometry and cellular assays

    PMID:34389713

    Open questions at the time
    • The downstream Wnt pathway branch mediating bone effects
    • Whether RSPO3 also acts on osteoclasts
  9. 2022 High

    LGR4 (not LGR5) was definitively identified as the RSPO3 receptor driving gastric stem cell proliferation and NF-κB-dependent inflammatory responses to H. pylori, and osteoblast-specific RSPO3 was shown to be required for full estrogenic effects on cortical bone.

    Evidence Conditional Lgr4 vs Lgr5 KO with H. pylori infection model and NF-κB reporters; osteoblast-specific Rspo3 KO with ovariectomy/estradiol rescue

    PMID:35068191 PMID:35767364

    Open questions at the time
    • Whether NF-κB activation is direct or secondary to Wnt signaling
    • Mechanism of RSPO3–estrogen interplay in cortical bone
  10. 2023 High

    A novel LGR4–Gab1–Gαi1/3 complex was identified as the effector of RSPO3-mediated Erk activation and neuroprotection, and RSPO3 was shown (with RSPO1) to be required for Ngn2+ sensory neural crest specification downstream of roof plate Wnt signaling.

    Evidence Co-IP of LGR4–Gab1–Gαi1/3, Gαi1/3 KO abolishing neuroprotection in MCAO model; Rspo1/Rspo3 double conditional KO with Ngn2 lineage tracing

    PMID:37767857 PMID:37805583

    Open questions at the time
    • Whether Gαi coupling occurs at other LGR4-expressing tissues
    • Redundancy between RSPO1 and RSPO3 in neural crest beyond Ngn2 lineage
    • Structural basis of LGR4–Gαi interaction
  11. 2024 Medium

    RSPO3 was linked to pulmonary endothelial regeneration via LGR4/ILK/β-catenin, a direct GNG7 interaction activating Akt/GSK-3β/β-catenin in gastric cancer, and hepatic metabolic zonation with inter-organ glucose regulation through the hepatic vagus nerve.

    Evidence EC-specific RSPO3 KO/overexpression in LPS model with ILK pathway assays; Co-IP/LC-MS/MS identifying GNG7 with siRNA epistasis; viral Rspo3 induction and Cre-LoxP suppression with vagal denervation in obese mice

    PMID:38581123 PMID:38677673 PMID:39854351

    Open questions at the time
    • Whether ILK pathway is distinct from β-catenin canonical signaling or convergent
    • GNG7 interaction requires independent replication
    • Neural circuit downstream of hepatic vagus is not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: (1) structural basis of RSPO3's selective engagement of different receptor complexes (SDC4, LGR4, LGR5, GNG7); (2) how tissue-specific cofactors determine canonical vs non-canonical pathway selection; (3) whether Gαi-coupled signaling is a general feature of RSPO3–LGR4 interactions beyond neurons.
  • No high-resolution structure of RSPO3 in complex with any receptor
  • No systematic comparison of downstream pathway activation across tissues
  • Relative in vivo contributions of ZNRF3/RNF43 clearance vs direct signaling remain unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0098772 molecular function regulator activity 5
Localization
GO:0005576 extracellular region 6
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1643685 Disease 5 GO:0060089 molecular transducer activity 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-1430728 Metabolism 2
Partners
GAB1GNAI1GNG7IQGAP1LGR4LGR5SDC4

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 RSPO3 binds syndecan 4 (SDC4) and together they activate Wnt/PCP signaling; RSPO3 functions by inducing SDC4-dependent, clathrin-mediated endocytosis, which is essential for PCP signal transduction via Fz7, Dvl, and JNK during Xenopus gastrulation and head cartilage morphogenesis Co-immunoprecipitation, loss-of-function in Xenopus embryos, pharmacological inhibition of clathrin-mediated endocytosis, epistasis with Wnt5a/Fz7/Dvl/JNK pathway components Developmental cell High 21397842
2016 Endothelial RSPO3 controls vascular remodeling through non-canonical WNT/Ca2+/NFAT signaling; inducible endothelial Rspo3 deletion causes apoptosis and vascular pruning; RSPO3 and EVI/WLS co-regulate RNF213, USP18, and TRIM30α, which target NFAT1 for proteasomal degradation, and NFAT protein levels are decreased in Rspo3-iECKO endothelial cells Inducible endothelial-specific Rspo3 knockout mice, genetic epistasis with Evi/Wls knockout, endothelial transcriptomic screen, pharmacological NFAT inhibition phenocopy Developmental cell High 26766444
2018 PDGFRα+ pericryptal stromal myofibroblasts are the critical in vivo source of RSPO3 and Wnts for intestinal stem cells; RSPO3 from these stromal cells is required for intestinal crypt Wnt/β-catenin signaling and Paneth cell differentiation, and is several orders of magnitude more potent than RSPO1 in stimulating organoid growth Cell-type-specific Cre-mediated Rspo3 excision in PdgfRα+ cells, organoid rescue assay with exogenous RSPO3 protein, DSS stress model Proceedings of the National Academy of Sciences of the United States of America High 29559533
2016 Capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate in the adrenal cortex; deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth, and RSPO3 is required in adult life for replenishment of lost cells and maintenance of zona glomerulosa identity Conditional Rspo3 knockout in adrenal capsule, immunofluorescence, β-catenin and SHH pathway readouts Genes & development High 27313319
2015 Targeting RSPO3 in PTPRK-RSPO3 fusion-positive colorectal xenografts inhibits tumor growth and promotes differentiation, with stem-cell-compartment genes being most sensitive; functional assays establish that RSPO3 drives stem-cell properties in these tumors Anti-RSPO3 antibody treatment of patient-derived xenografts, gene expression profiling, functional stem cell assays Nature High 26700806
2016 Conditional in vivo RSPO3 overexpression in Lgr5+ intestinal stem cells drives rapid development of hyperplastic, adenomatous, and adenocarcinomatous lesions, expanding Lgr5+ stem cells, Paneth cells, and niche compartments via increased Wnt/β-catenin signaling; mutant Kras synergizes with RSPO3 in hyperplastic growth Conditional Rspo3 transgenic mouse model crossed with Lgr5-GFP-CreERT2, histopathology, β-catenin signaling readouts Gut High 27511199
2020 RSPO3 acts through LGR4 to upregulate self-renewal genes and is essential for leukemia stem cell self-renewal in a subset of AML; blocking the RSPO3-LGR4 interaction with anti-RSPO3 antibody (rosmantuzumab) impairs self-renewal and induces differentiation in AML patient-derived xenografts without affecting normal hematopoietic stem cells; LGR4 is epigenetically upregulated and cooperates with HOXA9 Anti-RSPO3 antibody (OMP-131R10) treatment, patient-derived xenografts, LGR4 epigenetic upregulation analysis, HOXA9 cooperation assay Cancer cell High 32559496
2021 Osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and in a cell-autonomous manner increases osteoblast proliferation and differentiation to regulate vertebral trabecular bone mass and bone strength Osteoblast-specific Rspo3 conditional knockout (Runx2-cre), bone mass and strength measurements, cell proliferation and differentiation assays Nature communications High 34389713
2014 RSPO3 signals through LGR4 (with IQGAP1 as signaling mediator) to promote proliferation and migration of lung cancer cells; knockdown of RSPO3, LGR4, or IQGAP1 reduces cell proliferation and migration in vitro and tumor growth/metastasis in vivo shRNA knockdown, in vitro proliferation and migration assays, in vivo tumor and metastasis models Oncogene Medium 25531322
2017 RSPO3-LGR4 signaling inhibits osteogenic differentiation of human adipose-derived stem cells via suppression of ERK/FGF signaling; LGR4 silencing inhibits ERK signaling and osteogenic differentiation, and loss of LGR4 abrogates RSPO3-regulated osteogenesis and RSPO3-induced ERK1/2 signaling inhibition shRNA knockdown of RSPO3 and LGR4, ERK pathway inhibitors, osteogenic differentiation assays Scientific reports Medium 28220828
2020 RSPO3 (with RSPO1) signals through LGR4 to suppress hepatic cholesterol synthesis via activation of AMPKα (phosphorylation at Thr172) and consequent reduction of SREBP2 nuclear translocation; hepatic LGR4 knockdown increases cholesterol synthesis and decreases AMPKα phosphorylation In vivo Lgr4 and Rspo1/3 knockdown mice, AMPKα agonist/antagonist/shRNA epistasis, SREBP2 nuclear translocation assay FASEB journal Medium 32926477
2018 RSPO3 impairs barrier function of human vascular endothelial monolayers by inducing inter-endothelial gap formation through disruption of β-catenin and VE-cadherin alignment at adherens junctions, and synergizes with IL-1β to enhance permeability Electric Cell-substrate Impedance Sensing, immunofluorescence of β-catenin and VE-cadherin, primary human endothelial monolayers from multiple vascular beds Molecular medicine Medium 30157748
2022 RSPO3 signaling via LGR4 (not LGR5) drives proliferation of gastric stem cells and induces NF-κB activity in proliferative stem cells; upon H. pylori exposure, LGR4-driven NF-κB activation causes gland hyperplasia and chemokine expression leading to neutrophil recruitment Conditional Lgr4 and Lgr5 knockout mice, H. pylori infection model, NF-κB reporter assays, histology The EMBO journal High 35767364
2023 RSPO3 activates LGR4-Gab1-Gαi1/3 complex formation, leading to Erk activation and neuroprotection against ischemia/reperfusion injury; silencing or knockout of Gαi1/Gαi3 abolishes RSPO3-induced neuroprotection and Erk activation; endothelial RSPO3 protects neurons via this Gαi1/3-Erk axis in vivo Co-immunoprecipitation (LGR4-Gab1-Gαi1/3 complex), siRNA/KO of Gαi1/Gαi3, endothelial-specific RSPO3 KD/KO/overexpression mice, MCAO model, Erk pathway inhibitors Cell death & disease High 37805583
2024 RSPO3 mediates pulmonary endothelial regeneration in a LGR4-dependent manner; downstream effectors include both β-catenin and integrin-linked kinase (ILK)/Akt; EC-specific RSPO3 deletion inhibits endothelial proliferation and exacerbates injury, while overexpression promotes recovery EC-specific RSPO3 KD, inducible EC-specific KO, EC-specific overexpression mice, LPS endotoxemia model, ILK/Akt and β-catenin pathway assays International journal of biological macromolecules Medium 38677673
2024 RSPO3 interacts directly with GNG7 (G protein subunit gamma 7) as identified by Co-IP and LC-MS/MS; RSPO3 increases phosphorylation of Akt and GSK-3β and β-catenin expression in gastric cancer cells via GNG7, promoting cancer stem cell properties; GNG7 knockdown abolishes RSPO3-induced β-catenin activation Co-immunoprecipitation, LC-MS/MS proteomics, siRNA knockdown of GNG7, recombinant RSPO3 protein treatment, in vivo peritoneal seeding model Cancer medicine Medium 38581123
2023 The furin (FuFu) domains of RSPO3 mediate highly specific, LGR5-dependent cellular uptake when conjugated to liposomes, distinct from full-length RSPO1 which causes LGR5-independent uptake via heparan sulfate proteoglycans Liposome conjugation with RSPO3 furin domains vs full-length RSPO1, fluorescence uptake assays in LGR5-high vs LGR5-low cells, doxorubicin delivery functional assay Journal of controlled release Medium 36813038
2024 RSPO3 regulates NSCLC radioresistance by promoting pyroptosis via the β-catenin-NF-κB signaling pathway and NLRP3 inflammasome; anti-RSPO3 antibody blocks radiation-induced pyroptosis and anti-tumor immunity in vivo RSPO3 overexpression/knockdown, β-catenin-NF-κB pathway assays, NLRP3 inflammasome readouts, anti-RSPO3 antibody in vivo Radiotherapy and oncology Low 39245068
2020 RSPO3 expressed in subcutaneous adipocytes limits gluteofemoral adipose tissue expansion by suppressing adipogenesis and increasing gluteal adipocyte susceptibility to apoptosis, and promotes upper-body fat distribution by stimulating abdominal adipose progenitor proliferation; distinct responses are associated with differential WNT signaling; zebrafish with nonsense rspo3 mutation display altered fat distribution Human adipose progenitor cell culture assays, zebrafish rspo3 nonsense mutant, WNT signaling pathway readouts Nature communications Medium 32493999
2025 Hepatic Rspo3 regulates metabolic liver zonation (pericentral zone) and systemic glucose metabolism; viral induction of Rspo3 in obese mice improves insulin resistance and prevents body weight gain via neuronal inter-organ communication (hepatic vagus nerve); hepatic Rspo3 suppression via Cre-LoxP causes glucose intolerance, insulin resistance, fatty liver, and obesity Viral-mediated Rspo3 induction, Cre-LoxP conditional suppression, hepatic vagal denervation, metabolic phenotyping PLoS biology Medium 39854351
2022 Osteoblast-derived RSPO3 is required for a full estrogenic effect on cortical (but not trabecular) bone; estradiol and RSPO3 regulate vertebral trabecular bone mass independently of each other, established by epistasis using osteoblast-specific RSPO3 knockout mice Osteoblast-specific Rspo3 KO (Runx2-cre), ovariectomy + estradiol rescue, bone mass and strength measurements American journal of physiology. Endocrinology and metabolism Medium 35068191
2017 Loss of AXIN1 (via frameshift deletions) confers resistance to WNT pathway blockade (porcupine inhibitor LGK974) in RSPO3-fusion-positive colorectal cancer cells; AXIN1 suppression by RNAi in parental VACO6 cells (PTPRK-RSPO3 fusion) recapitulates resistance Long-term drug selection in RSPO3-fusion CRC cell lines, whole exome sequencing of resistant clones, RNAi validation EMBO molecular medicine Medium 28100566
2023 Rspo1 and Rspo3 are co-expressed with Wnt1/Wnt3a in the roof plate and are required for specification of Ngn2-positive sensory lineage neural crest cells; Rspo1/Rspo3 double knockout partially phenocopies Wnt1/Wnt3a double knockout for this specific neural crest subtype Rspo1/Rspo3 double conditional knockout mice, Ngn2 lineage tracing, Wnt/β-catenin reporter assay, comparison with Wnt1/Wnt3a dKO Developmental dynamics Medium 37767857

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 PDGFRα pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo. Proceedings of the National Academy of Sciences of the United States of America 232 29559533
2015 Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature 202 26700806
2011 Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis. Developmental cell 192 21397842
2016 Endothelial RSPO3 Controls Vascular Stability and Pruning through Non-canonical WNT/Ca(2+)/NFAT Signaling. Developmental cell 149 26766444
2016 Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma. The Journal of pathology 107 26924569
2020 Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia. Cancer cell 94 32559496
2016 The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3. Genes & development 75 27313319
2016 RSPO3 expands intestinal stem cell and niche compartments and drives tumorigenesis. Gut 64 27511199
2014 Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness. Oncogene 63 25531322
2017 Loss of AXIN1 drives acquired resistance to WNT pathway blockade in colorectal cancer cells carrying RSPO3 fusions. EMBO molecular medicine 55 28100566
2020 RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro. Nature communications 49 32493999
2017 RSPO3-LGR4 Regulates Osteogenic Differentiation Of Human Adipose-Derived Stem Cells Via ERK/FGF Signalling. Scientific reports 47 28220828
2017 RSPO3 antagonism inhibits growth and tumorigenicity in colorectal tumors harboring common Wnt pathway mutations. Scientific reports 39 29127379
2012 A conditional allele of Rspo3 reveals redundant function of R-spondins during mouse limb development. Genesis (New York, N.Y. : 2000) 35 22610508
2021 RSPO3 is important for trabecular bone and fracture risk in mice and humans. Nature communications 29 34389713
2022 Gastric stem cells promote inflammation and gland remodeling in response to Helicobacter pylori via Rspo3-Lgr4 axis. The EMBO journal 24 35767364
2019 RSPO3 promotes the aggressiveness of bladder cancer via Wnt/β-catenin and Hedgehog signaling pathways. Carcinogenesis 20 30329043
2020 Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKα-SREBP2 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 32926477
2020 RSPO3 is a marker candidate for predicting tumor aggressiveness in ovarian cancer. Annals of translational medicine 16 33313096
2018 RSPO3 impairs barrier function of human vascular endothelial monolayers and synergizes with pro-inflammatory IL-1. Molecular medicine (Cambridge, Mass.) 16 30157748
2023 Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury. Cell death & disease 15 37805583
2024 Endothelial RSPO3 mediates pulmonary endothelial regeneration by LGR4-dependent activation of β-catenin and ILK signaling pathways after inflammatory vascular injury. International journal of biological macromolecules 12 38677673
2024 RSPO3 regulates the radioresistance of Non-Small cell lung cancer cells via NLRP3 Inflammasome-Mediated pyroptosis. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 11 39245068
2021 Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state. Stem cell research & therapy 7 34099046
2022 Estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other. American journal of physiology. Endocrinology and metabolism 6 35068191
2022 RSPO3 is a novel contraction-inducible factor identified in an "in vitro exercise model" using primary human myotubes. Scientific reports 6 35995979
2025 Rspo3-mediated metabolic liver zonation regulates systemic glucose metabolism and body mass in mice. PLoS biology 5 39854351
2018 Cynoglossus semilaevis Rspo3 Regulates Embryo Development by Inhibiting the Wnt/β-Catenin Signaling Pathway. International journal of molecular sciences 5 29966290
2017 The RSPO3 gene as genetic markers for bone mass assessed by quantitative ultrasound in a population of young adults. Annals of human genetics 5 29230809
2024 RSPO3 induced by Helicobacter pylori extracts promotes gastric cancer stem cell properties through the GNG7/β-catenin signaling pathway. Cancer medicine 4 38581123
2023 RSPO3 Furin domain-conjugated liposomes for selective drug delivery to LGR5-high cells. Journal of controlled release : official journal of the Controlled Release Society 4 36813038
2023 Amniotic fluid stem cell attenuated necrotizing enterocolitis progression by promoting Rspo3/AMPKα axis. Immunobiology 4 37173190
2023 Upregulation of RSPO3 via targeted promoter DNA demethylation inhibits the progression of cholangiocarcinoma. Clinical epigenetics 4 37932819
2025 RSPO3 Promotes Proliferation and Self-Renewal of Limbal Epithelial Stem Cells Through a WNT/β-Catenin-Independent Signaling Pathway. Investigative ophthalmology & visual science 2 39760688
2022 Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer. PloS one 2 36129915
2025 Lonicerin targets ADRA1D and RSPO3 to ameliorate diabetes-induced vascular injury through Ca2+/Calcineurin/NFAT1-dependent anti-EndMT pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 1 40398181
2025 H3K4me3 regulates the transcription of RSPO3 in dermal papilla cells to influence hair follicle morphogenesis and development. Epigenetics & chromatin 1 40775776
2024 Decreased RSPO3 and β-Catenin in Preeclampsia: Correlation with Blood Pressure and Pregnancy Outcomes. Medical science monitor : international medical journal of experimental and clinical research 1 39568191
2023 Rspo1 and Rspo3 are required for sensory lineage neural crest formation in mouse embryos. Developmental dynamics : an official publication of the American Association of Anatomists 1 37767857
2026 Deletion of Rspo1 or Rspo3 in the mesenchyme does not affect Wolffian duct maintenance or morphogenesis. microPublication biology 0 41573670
2026 NsPEFs-enriched ADSCs-EVs alleviate osteoarthritis via RSPO3-mediated dual pro-chondrogenic and pro-M2 macrophage properties. Bioactive materials 0 41624077
2025 Protein interaction network drive more group integrated analytic larynx hub protein markers: LYVE1/FBLN5/INMT/DCN/ZFY/RSPO3 protein macromolecule collaborative diagnosis of a new era. International journal of biological macromolecules 0 40419046
2025 Unveiling CTRB2, RSPO3, KLOTB, and ROR1 as obesity-pancreatic disease association proteins: a comprehensive Mendelian randomization study. Gastroenterology report 0 40860620
2025 RSPO3 rearrangements in advanced colorectal cancer patients and their relationship with disease characteristics. World journal of gastrointestinal oncology 0 41281482