ArticlePloS one2012
Wnt activation by wild type and mutant myocilin in cultured human trabecular meshwork cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Dexamethasone Modulates the Dynamics of Wnt Signaling in Human Trabecular Meshwork Cells.Vision (Basel, Switzerland) · 2023Article
- Transgenic Overexpression of Myocilin Leads to Variable Ocular Anterior Segment and Retinal Alterations Associated with Extracellular Matrix Abnormalities in Adult Zebrafish.International journal of molecular sciences · 2022Article
- Serum circulating proteins from pediatric patients with dilated cardiomyopathy cause pathologic remodeling and cardiomyocyte stiffness.JCI insight · 2021Article
- Molecular architecture and modifications of full-length myocilin.Experimental eye research · 2021Article
- Knockout ofBiology · 2021Article
- Myocilin-associated Glaucoma: A Historical Perspective and Recent Research Progress.Molecular vision · 2021Review
- Wnt Activation After Inhibition Restores Trabecular Meshwork Cells Toward a Normal Phenotype.Investigative ophthalmology & visual science · 2020Article
- Extracellular vesicle-mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling.Journal of cellular and molecular medicine · 2020Article
- Generating cell-derived matrices from human trabecular meshwork cell cultures for mechanistic studies.Methods in cell biology · 2020Article
- RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations.Journal of the American Heart Association · 2019Article
- Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior.Acta biomaterialia · 2018Article
- Identification of myocilin as a blood plasma protein and analysis of its role in leukocyte adhesion to endothelial cell monolayers.PloS one · 2018Article
- Small-molecule inhibition of Wnt signaling abrogates dexamethasone-induced phenotype of primary human trabecular meshwork cells.Experimental cell research · 2017Article
- Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.Progress in retinal and eye research · 2017Review
- Extracellular vesicles mediate signaling between the aqueous humor producing and draining cells in the ocular system.PloS one · 2017Article
- Genetic architecture of natural variation in visual senescence in Drosophila.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Apigenin suppresses colorectal cancer cell proliferation, migration and invasion via inhibition of the Wnt/β-catenin signaling pathway.Oncology letters · 2016Article
- Glaucomatous MYOC mutations activate the IL-1/NF-κB inflammatory stress response and the glaucoma marker SELE in trabecular meshwork cells.Molecular vision · 2015Article
- Canonical wnt signaling regulates extracellular matrix expression in the trabecular meshwork.Investigative ophthalmology & visual science · 2014Article
- Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2.Investigative ophthalmology & visual science · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMyocilin is a gene linked to the most prevalent form of glaucoma, a major blinding disease. The trabecular meshwork (TM), a specialized eye tissue, is believed to be involved, at least in part, in the development of glaucoma. The Pro³⁷⁰ to Leu (P370L) mutation of myocilin is associated with severe glaucoma phenotypes and Gln³⁶⁸ stop (Q368X) is the most common myocilin mutation reported. Myocilin, upon overexpression, has been shown to induce phenotypes that include a loss of actin stress fibers, an increase in the cAMP level and protein kinase A (PKA) activity, as well as a reduction in the RhoA activity. We examined herein whether Wnt signaling pathway is involved in the myocilin phenotypes and whether P370L and Q368X mutants also display biological effects similar to those of the wild type myocilin. METHODOLOGY/PRINCIPAL
findingsWild type myocilin, when transfected into cultured human TM cells, induced a loss of actin stress fibers as judged by phalloidin staining. Such a loss was averted by treatment of secreted Frizzled-related protein 1 (sFRP1), an inhibitor of Wnt signaling. Consistent with the notion that Wnt pathway mediates the myocilin phenotype, Wnt activation was demonstrated by TOP/FOP-Flash reporter assays. Treatment of human TM cells of a Wnt activator, SB216763, as well as transfection of myocilin P370L and Q368X mutants all resulted in actin stress fiber loss, PKA activation and RhoA inactivation. The PKA elevation was obviated by the sFRP1 treatment, indicating that Wnt signaling was upstream that of PKA. CONCLUSIONS/SIGNIFICANCE: The present study demonstrated that following forced expression of wild type myocilin, Wnt was activated, triggering in turn other myocilin-related alterations. P370L and Q368X mutations induced similar phenotypes, suggesting one possible mechanism how the mutants may lead to TM cell damage and pathology.
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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.