ArticleMolecular and cellular biology2011
Identification of a novel inhibitor of the canonical Wnt pathway.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 126 citations in OpenAlex.
- Complexity of PEDF multifunctional signaling in retinal development and diseases.Communications biology · 2026Article
- The gut-liver axis modulates intestinal immune homeostasis.Mucosal immunology · 2026Review
- Influence of pigment epithelium-derived factors on HBiological research · 2025Article
- Elevated PEDF promotes the occurrence of diabetes mellitus via suppressing GSIS by downregulating the SNARE complex.Communications biology · 2025Article
- Functional Roles of Pigment Epithelium-Derived Factor in Retinal Degenerative and Vascular Disorders: A Scoping Review.Investigative ophthalmology & visual science · 2024Article
- Article
- Genetic variants and altered expression of SERPINF1 confer disease susceptibility in patients with otosclerosis.Journal of human genetics · 2023Article
- Receptors that bind to PEDF and their therapeutic roles in retinal diseases.Frontiers in endocrinology · 2023Review
- The Contribution of Wnt Signaling to Vascular Complications in Type 2 Diabetes Mellitus.International journal of molecular sciences · 2022Review
- Curcumin and Wnt/β‑catenin signaling in exudative age‑related macular degeneration (Review).International journal of molecular medicine · 2022Review
- Wnt/frizzled Signaling in Endothelium: A Major Player in Blood-Retinal- and Blood-Brain-Barrier Integrity.Cold Spring Harbor perspectives in medicine · 2022Review
- Rhein for treating diabetes mellitus: A pharmacological and mechanistic overview.Frontiers in pharmacology · 2022Review
- Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy.Frontiers in cell and developmental biology · 2022Article
- Severe types of fetopathy are associated with changes in the serological proteome of diabetic mothers.Medicine · 2021Observational
- Antiangiogenic therapy in diabetic nephropathy: A double‑edged sword (Review).Molecular medicine reports · 2021Review
- Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice.Frontiers in pharmacology · 2021Review
- Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond.Frontiers in cell and developmental biology · 2021Review
- Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons.International journal of molecular sciences · 2020Article
- Elevated pigment epithelium-derived factor induces diabetic erectile dysfunction via interruption of the Akt/Hsp90β/eNOS complex.Diabetologia · 2020Article
- Inhibition of retinal neovascularization by a PEDF-derived nonapeptide in newborn mice subjected to oxygen-induced ischemic retinopathy.Experimental eye research · 2020Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Wnt signaling is known to regulate multiple processes including angiogenesis, inflammation, and fibrosis. Here, we identified a novel inhibitor of the Wnt pathway, pigment epithelium-derived factor (PEDF), a multifunctional serine proteinase inhibitor. Both overexpression of PEDF in transgenic mice and administration of PEDF protein attenuated Wnt signaling induced by retinal ischemia. Furthermore, PEDF knockdown by small interfering RNA (siRNA) and PEDF knockout in PEDF(-/-) mice induced activation of Wnt signaling. PEDF bound to LRP6, a Wnt coreceptor, with high affinity (K(d) [dissociation constant] of 3.7 nM) and blocked the Wnt signaling induced by Wnt ligand. The physical interaction of PEDF with LRP6 was confirmed by a coprecipitation assay, which showed that PEDF bound to LRP6 at the E1E2 domain. In addition, binding of PEDF to LRP6 blocked Wnt ligand-induced LRP6-Frizzled receptor dimerization, an essential step in Wnt signaling. These results suggest that PEDF is an endogenous antagonist of LRP6, and blocking Wnt signaling may represent a novel mechanism for its protective effects against diabetic retinopathy.
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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.