ArticleProceedings of the National Academy of Sciences of the United States of America2010
Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 84 citations in OpenAlex.
- SerpinA3 is an Endogenous TGF-β Receptor Antagonist that Attenuates Cardiac Fibroblast Activation and Fibrotic Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Canonical WNT signalling governs Echinococcus metacestode development.PLoS pathogens · 2026Article
- The Therapeutic Effect of a Biodegradable Long-Acting Intravitreal Implant Containing CGK012 on Neovascular Age-Related Macular Degeneration by Promoting β-Catenin Degradation.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Hepatocyte KCTD17-mediated SERPINA3 inhibition determines liver fibrosis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2025Article
- Serpina3k lactylation protects from cardiac ischemia reperfusion injury.Nature communications · 2025Article
- Multi-omics approaches for biomarker discovery and precision diagnosis of prediabetes.Frontiers in endocrinology · 2025Review
- Integrative analysis of PANoptosis-related genes in diabetic retinopathy: machine learning identification and experimental validation.Frontiers in immunology · 2024Article
- Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal.International urology and nephrology · 2023Article
- SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.International journal of molecular sciences · 2023Article
- Targeting Wnt-β-Catenin Signaling Pathway for Hepatocellular Carcinoma Nanomedicine.Gastro hep advances · 2023Review
- The versatile role of Serpina3c in physiological and pathological processes: a review of recent studies.Frontiers in endocrinology · 2023Review
- Kallistatin prevents ovarian hyperstimulation syndrome by regulating vascular leakage.Journal of cellular and molecular medicine · 2022Article
- Wnt/frizzled Signaling in Endothelium: A Major Player in Blood-Retinal- and Blood-Brain-Barrier Integrity.Cold Spring Harbor perspectives in medicine · 2022Review
- Distinct roles of LRP5 and LRP6 in Wnt signaling regulation in the retina.Biochemical and biophysical research communications · 2021Article
- Diabetes-induced upregulation of kallistatin levels exacerbates diabetic nephropathy via RAS activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Proteome characterization of small extracellular vesicles from spared nerve injury model of neuropathic pain.Journal of proteomics · 2020Article
- Fenofibrate prevents iron induced activation of canonical Wnt/β-catenin and oxidative stress signaling in the retina.NPJ aging and mechanisms of disease · 2020Article
- Wnt Signaling in vascular eye diseases.Progress in retinal and eye research · 2019Review
- Canonical Wnt signaling in diabetic retinopathy.Vision research · 2017Review
- Proteomic analysis of serum biomarkers for prediabetes using the Long-Evans Agouti rat, a spontaneous animal model of type 2 diabetes mellitus.Journal of diabetes investigation · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
The Wnt pathway regulates multiple biological and pathological processes including angiogenesis and inflammation. Here we identified a unique inhibitor of the Wnt pathway, SERPINA3K, a serine proteinase inhibitor with anti-inflammatory and angiogenic activities. SERPINA3K blocked the Wnt pathway activation induced by a Wnt ligand and by diabetes. Coprecipitation and ligand binding assay showed that SERPINA3K binds to low-density lipoprotein receptor-like protein 6 (LRP6) with a K(d) of 10 nM, in the range of its physiological concentration in the retina. Under the same conditions, SERPINA3K did not bind to the frizzled (Fz) receptor or low-density lipoprotein receptor. Further, SERPINA3K bound to LRP6 at the extracellular domain and blocked its dimerization with the Fz receptor induced by a Wnt ligand. The antagonizing activity of SERPINA3K to LRP6 was further confirmed by Xenopus axis duplication assay. These results suggest that SERPINA3K is a high-affinity, endogenous antagonist of LRP6. The blockade of Wnt signaling may represent a unifying mechanism for the anti-inflammatory and anti-angiogenic effects of SERPINA3K.
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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.