NDLI: Epithelial-mesenchymal transition-like phenotypic changes of retinal pigment epithelium induced by TGF-ß are prevented by PPAR-Î³ agonists.

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Epithelial-mesenchymal transition-like phenotypic changes of retinal pigment epithelium induced by TGF-ß are prevented by PPAR-Î³ agonists.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Koizumi, Noriko Okumura, Naoki Mizuhara, Eri Kay, EunDuck P. Kinoshita, Shigeru Hamuro, Junji Hatanaka, Hiroki
Description	Country affiliation: Japan Author Affiliation: Hatanaka H ( Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.)
Abstract	PURPOSE: Proliferative eye diseases, such as proliferative vitreoretinopathy and proliferative diabetic retinopathy, are caused partly by fibrotic change of retinal pigment epithelial cells (RPECs). The purpose of our study was to examine the effect of the peroxisome proliferator-activated receptor-Î³ (PPAR-Î³) agonist on the fibrotic change of primate RPECs. METHODS: Monkey RPECs (MRPECs) isolated from a cynomolgus monkey eye were subcultured. To induce fibrotic change, MRPECs were cultured with TGF-ß2 (3 ng/mL), and also cultured in the coexistence of TGF-ß2 and the PPAR-Î³ agonist pioglitazone (30 µM). The phenotype of the cultured MRPECs was evaluated by phase contrast microscopy and immunocytochemical analysis. The phosphorylation of Smad2/Smad3 proteins was examined by Western blot analysis. RESULTS: Primary MRPECs were cultured as a monolayer with a hexagonal cell shape, and positive expression of ZO-1, Na(+)/K(+)-ATPase, and RPE65 was confirmed. Cell morphology and the expression of these markers were maintained in the presence of pioglitazone, whereas the cells were elongated and the expression of these markers was reduced in its absence. Conversely, the expression of phalloidin, -smooth muscle actin, and fibronectin was reduced in the presence of pioglitazone, whereas it was increased in the absence. Western blot assay demonstrated that phosphorylation of Smad2/Smad3 proteins was suppressed by pioglitazone. CONCLUSIONS: The PPAR-Î³ agonist pioglitazone inhibited the fibrotic change of primary MRPECs through the suppression of TGF-ß signaling. Pioglitazone might prove to be a clinically applicable and effective pharmaceutic treatment for proliferative eye diseases.
ISSN	01460404
e-ISSN	15525783
Journal	Investigative Opthalmology & Visual Science
Issue Number	11
Volume Number	53
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2012-10-05
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Epithelial-mesenchymal Transition Drug Effects Hypoglycemic Agents Pharmacology Agonists Retinal Pigment Epithelium Thiazolidinediones Transforming Growth Factor Beta2 Animals Blotting, Western Cell Shape Cells, Cultured Immunohistochemistry Macaca Fascicularis Microscopy, Phase-contrast Phenotype Phosphorylation Metabolism Reverse Transcriptase Polymerase Chain Reaction Smad2 Protein Genetics Smad3 Protein Sodium-potassium-exchanging Atpase Zonula Occludens-1 Protein Cis-trans-isomerases Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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