ArticlePloS one2020
Targeting the Wnt signaling pathway through R-spondin 3 identifies an anti-fibrosis treatment strategy for multiple organs.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
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- Comprehensive circRNA expression profile and hub genes screening during human liver development.Annals of medicine · 2025Article
- Spatially resolved multi-omics of human metabolic dysfunction-associated steatotic liver disease.Nature genetics · 2025Article
- Discovery of novel diagnostic biomarkers of hepatocellular carcinoma associated with immune infiltration.Annals of medicine · 2025Article
- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Impairment of stromal-epithelial regenerative cross-talk in Hirschsprung disease primes for the progression to enterocolitis.Science translational medicine · 2025Article
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- Advances in the development of Wnt/β-catenin signaling inhibitors.RSC medicinal chemistry · 2025Review
- Deep topic modeling of spatial transcriptomics in the rheumatoid arthritis synovium identifies distinct classes of ectopic lymphoid structures.bioRxiv : the preprint server for biology · 2025Article
- Identification and validation of plasma AGRN as a novel diagnostic biomarker of hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis.Histology and histopathology · 2024Article
- Progranulin: A promising biomarker and therapeutic target for fibrotic diseases.Acta pharmaceutica Sinica. B · 2024Review
- Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?Pharmaceuticals (Basel, Switzerland) · 2024Review
- RSPO3 induced by Helicobacter pylori extracts promotes gastric cancer stem cell properties through the GNG7/β-catenin signaling pathway.Cancer medicine · 2024Article
- Identifying novel potential drug targets for endometriosis via plasma proteome screening.Frontiers in endocrinology · 2024Article
- How single-cell transcriptomics provides insight on hepatic responses to TCDD.Current opinion in toxicology · 2023Article
- R-spondin family biology and emerging linkages to cancer.Annals of medicine · 2023Review
- Article
- Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Wnt/β-catenin signaling pathway has been implicated in human proliferative diseases such as cancer and fibrosis. The functions of β-catenin and several other components of this pathway have been investigated in fibrosis. However, the potential role of R-spondin proteins (RSPOs), enhancers of the Wnt/β-catenin signaling, has not been described. A specific interventional strategy targeting this pathway for fibrosis remains to be defined. We developed monoclonal antibodies against members of the RSPO family (RSPO1, 2, and 3) and probed their potential function in fibrosis in vivo. We demonstrated that RSPO3 plays a critical role in the development of fibrosis in multiple organs. Specifically, an anti-RSPO3 antibody, OMP-131R10, when dosed therapeutically, attenuated fibrosis in carbon tetrachloride (CCl4)-induced liver fibrosis, bleomycin-induced pulmonary and skin fibrosis models. Mechanistically, we showed that RSPO3 induces multiple pro-fibrotic chemokines and cytokines in Kupffer cells and hepatocytes. We found that the anti-fibrotic activity of OMP-131R10 is associated with its inhibition of β-catenin activation in vivo. Finally, RSPO3 was found to be highly elevated in the active lesions of fibrotic tissues in mouse models of fibrosis and in patients with idiopathic pulmonary fibrosis (IPF) and nonalcoholic steatohepatitis (NASH). Together these data provide an anti-fibrotic strategy for targeting the Wnt/β-catenin pathway through RSPO3 blockade and support that OMP-131R10 could be an important therapeutic agent for fibrosis.
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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.