PMID: 9185044Jun 1, 1997Paper

PAF antagonists as possible inhibitors of corneal epithelial defects and ulceration

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
H E Bazan, Y Tao

Abstract

The extracellular matrix (ECM) plays a crucial role in cell adhesion, differentiation and wound-healing. Its stability is tightly controlled by enzymes that regulate the metabolism of its components (e.g collagen, fibronectin, laminin). We have found that in the cornea, a potent lipid inflammatory mediator platelet-activating factor (PAF) activates the expression of two metalloproteinases (MMP-1 and MMP-9) as well as urokinase-plasminogen activator (uPA). uPA is of particular interest because, as a serine protease, it is at the top of the protease cascade. PAF may contribute to the destruction of the ECM and the formation of epithelial defects and corneal ulcers by activating uPA and then proteases. We also investigated how several PAF antagonists with different binding affinities can block the expression of the uPA gene. Our results suggest that PAF antagonists with affinities for intracellular binding sites and/or specific structures derived from triazolobenzodiazepine could be of therapeutic use to limit the breakdown of the ECM and the development of ulcer formation.

References

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Jul 1, 1993·Experimental Eye Research·Y ItoK Saito

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Citations

Sep 30, 2010·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Na LiHaydee E P Bazan
Jul 5, 2005·Expert Opinion on Investigational Drugs·M Hingorani
Mar 6, 2012·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Hugh CalkinsDavid Wilber
Dec 29, 2020·Prostaglandins & Other Lipid Mediators·Barbara DalmasoCarolina Beltrame Del Debbio

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