FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost

Investigative Ophthalmology & Visual Science
Lance P DoucetteM A Walter

Abstract

This study examines the effect of FOXC1 on the prostaglandin pathway in order to explore FOXC1's role in the prostaglandin-resistant glaucoma phenotype commonly seen in Axenfeld-Rieger syndrome. Binding and transcriptional activity of FOXC1 to the gene coding for the EP3 prostaglandin receptor (PTGER3) were evaluated through ChIP-qPCR and luciferase-based assays. Immortalized trabecular meshwork cells (TM1) and HeLa cells had FOXC1 mRNA reduced via siRNA interference. qPCR and Western blot experiments were conducted to examine the changes in prostaglandin receptor expression brought about by lowered FOXC1. TM1 cells were then treated with 10 μM latanoprost acid and/or an siRNA for FOXC1. The expression of fibronectin and matrix metalloproteinase 9 were evaluated via qPCR in each treatment condition. ChIP-qPCR and luciferase experiments confirmed that FOXC1 binds to and activates transcription of the EP3 gene prostaglandin receptor. qPCR and Western experiments in HeLa and TM1 cells showed that FOXC1 siRNA knockdown results in significantly lowered EP3 levels (protein and RNA). In addition, RNA levels of the other prostaglandin receptor genes EP1 (PTGER1), EP2 (PTGER2), EP4 (PTGER4), and FP (PTGFR) were altered when FOXC1 was kn...Continue Reading

References

Nov 1, 1990·Prostaglandins, Leukotrienes, and Essential Fatty Acids·R W NorrdinW B High
Oct 1, 1989·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·I R Garrett, G R Mundy
Oct 1, 1987·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·U H Lerner
Jun 1, 1970·Endocrinology·D C Klein, L G Raisz
Dec 13, 1972·Nature: New Biology·S H Ferreira
Mar 16, 2002·The Annals of Pharmacotherapy·Christy L AlexanderSteven R Abel
Oct 9, 2002·Archives of Ophthalmology·Anders HeijlUNKNOWN Early Manifest Glaucoma Trial Group
Oct 27, 2004·Investigative Ophthalmology & Visual Science·Yahya TamimiMichael A Walter
Aug 4, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Burkhard HinzKay Brune
Feb 21, 2006·The British Journal of Ophthalmology·H A Quigley, A T Broman
Aug 1, 2006·Investigative Ophthalmology & Visual Science·Takashi OtaMakoto Araie
Jan 2, 2007·Investigative Ophthalmology & Visual Science·M Hermina StrungaruMichael A Walter
Oct 31, 2008·Investigative Ophthalmology & Visual Science·Alice L YuUlrich Welge-Lüssen
May 4, 2010·Investigative Ophthalmology & Visual Science·W Daniel StamerDavid F Woodward
Sep 21, 2013·Translational Vision Science & Technology·Alex L C TamYeni H Yücel
Jun 4, 2014·Molecular and Cellular Biochemistry·Xiang-pan KongRong-fa Bu
Apr 25, 2015·Survey of Ophthalmology·Lance P DoucetteMichael A Walter
Apr 14, 2016·Ophthalmic Genetics·Lance P Doucette, Michael A Walter
Jun 22, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yu-Zhong XuXiao-Jun Li
Oct 4, 2017·Clinical Genetics·M Seifi, M A Walter
Mar 1, 2018·Oncotarget·Fahed A ElianMichael A Walter

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