ArticleScientific reports2020
Tissue-targeted R-spondin mimetics for liver regeneration.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- A Targeted R-Spondin Mimetic Induces Hepatocyte-Specific Activation of Wnt Signaling and Cell Proliferation in Mice.Gastro hep advances · 2026Article
- R-spondin 2 suppresses hepatic steatosis via activation of AMPK-ACC signaling.JHEP reports : innovation in hepatology · 2025Article
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025Review
- Design principles and therapeutic applications of novel synthetic WNT signaling agonists.iScience · 2024Review
- Article
- A WNT mimetic with broad spectrum FZD-specificity decreases fibrosis and improves function in a pulmonary damage model.Respiratory research · 2024Article
- Enhancing precision in colorectal cancer surgery: development of an LGR5-targeting RSPO1 peptide mimetic as a contrast agent for intraoperative fluorescence molecular imaging.Cell cycle (Georgetown, Tex.) · 2024Article
- BRAIDing receptors for cell-specific targeting.eLife · 2024Article
- Effects of Fc glycosylation on the activity of WNT mimetic agonistic antibodies.Antibody therapeutics · 2024Article
- Distinct hepatocyte identities in liver homeostasis and regeneration.JHEP reports : innovation in hepatology · 2023Review
- Therapeutic blood-brain barrier modulation and stroke treatment by a bioengineered FZDNature communications · 2023Article
- Exploiting the Receptor-Binding Domains of R-Spondin 1 to Target Leucine-Rich Repeat-Containin G-Coupled Protein Receptor 5-Expressing Stem Cells in Ovarian Cancer.The Journal of pharmacology and experimental therapeutics · 2023Article
- A Spatial Atlas of Wnt Receptors in Adult Mouse Liver.The American journal of pathology · 2023Article
- Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis.Blood advances · 2023Article
- Selective Activation of the Wnt-Signaling Pathway as a Novel Therapy for the Treatment of Diabetic Retinopathy and Other Retinal Vascular Diseases.Pharmaceutics · 2022Review
- Single-cell spatial transcriptomics reveals a dynamic control of metabolic zonation and liver regeneration by endothelial cell Wnt2 and Wnt9b.Cell reports. Medicine · 2022Article
- SZN-413, a FZD4 Agonist, as a Potential Novel Therapeutic for the Treatment of Diabetic Retinopathy.Translational vision science & technology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
R-spondin (RSPO) proteins amplify Wnt signaling and stimulate regeneration in a variety of tissues. To repair tissue in a tissue-specific manner, tissue-targeted RSPO mimetic molecules are desired. Here, we mutated RSPO (RSPO2 F105R/F109A) to eliminate LGR binding while preserving ZNRF3/RNF43 binding and targeted the mutated RSPO to a liver specific receptor, ASGR1. The resulting bi-specific molecule (αASGR1-RSPO2-RA) enhanced Wnt signaling effectively in vitro, and its activity was limited to ASGR1 expressing cells. Systemic administration of αASGR1-RSPO2-RA in mice specifically upregulated Wnt target genes and stimulated cell proliferation in liver but not intestine (which is more responsive to non-targeted RSPO2) in healthy mice, and improved liver function in diseased mice. These results not only suggest that a tissue-specific RSPO mimetic protein can stimulate regeneration in a cell-specific manner, but also provide a blueprint of how a tissue-specific molecule might be constructed for applications in a broader context.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.