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Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts
PURPOSE: The transformation of quiescent keratocytes to active phenotypes and the ensuing fibrotic response play important roles in corneal scar formation. This study aims to observe the antifibrotic effect of peroxisome proliferator-activated receptor-γ (PPARγ) agonist on corneal fibroblasts cultur...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Molecular Vision
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776343/ https://www.ncbi.nlm.nih.gov/pubmed/19936025 |
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author | Pan, Hongwei Chen, Jiansu Xu, Jintang Chen, Miaojiao Ma, Rong |
author_facet | Pan, Hongwei Chen, Jiansu Xu, Jintang Chen, Miaojiao Ma, Rong |
author_sort | Pan, Hongwei |
collection | PubMed |
description | PURPOSE: The transformation of quiescent keratocytes to active phenotypes and the ensuing fibrotic response play important roles in corneal scar formation. This study aims to observe the antifibrotic effect of peroxisome proliferator-activated receptor-γ (PPARγ) agonist on corneal fibroblasts cultured in vitro, and to explore the potential application of peroxisome proliferator-activated receptor agonist to the prevention of corneal opacity following wound repair. METHODS: Rabbit corneal keratocytes were cultured in a medium containing 10% serum to induce their transformation to fibroblasts and myofibroblasts, which are similar to those that repair corneas. After incubation with the PPARγ agonist pioglitazone at different concentrations, the effect of pioglitazone on the migration, contractility, and viability of corneal fibroblasts was examined. The secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 was determined by gelatin zymography, and the synthesis of collagen I and fibronectin was investigated by western blotting. RESULTS: Treatment with pioglitazone at concentrations ranging from 1 to 10 μm significantly decreased corneal fibroblast migration, as determined by scrape-wound assay, inhibited corneal fibroblast-induced collagen lattice contraction, and reduced MMP-2 and MMP-9 secretion into the supernatant of cell cultures in a dose-dependent manner. The expression of fibronectin was significantly decreased, while the expression of collagen I was only decreased when treated with 10 μm pioglitazone. Cell viability was not evidently changed compared to the control. CONCLUSION: This in vitro study demonstrated the anti-fibrotic effect of pioglitazone, suggesting that activation of PPARγ may be a new approach for the treatment of corneal opacity and scar formation in the corneal wound healing process. |
format | Text |
id | pubmed-2776343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Molecular Vision |
record_format | MEDLINE/PubMed |
spelling | pubmed-27763432009-11-20 Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts Pan, Hongwei Chen, Jiansu Xu, Jintang Chen, Miaojiao Ma, Rong Mol Vis Research Article PURPOSE: The transformation of quiescent keratocytes to active phenotypes and the ensuing fibrotic response play important roles in corneal scar formation. This study aims to observe the antifibrotic effect of peroxisome proliferator-activated receptor-γ (PPARγ) agonist on corneal fibroblasts cultured in vitro, and to explore the potential application of peroxisome proliferator-activated receptor agonist to the prevention of corneal opacity following wound repair. METHODS: Rabbit corneal keratocytes were cultured in a medium containing 10% serum to induce their transformation to fibroblasts and myofibroblasts, which are similar to those that repair corneas. After incubation with the PPARγ agonist pioglitazone at different concentrations, the effect of pioglitazone on the migration, contractility, and viability of corneal fibroblasts was examined. The secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 was determined by gelatin zymography, and the synthesis of collagen I and fibronectin was investigated by western blotting. RESULTS: Treatment with pioglitazone at concentrations ranging from 1 to 10 μm significantly decreased corneal fibroblast migration, as determined by scrape-wound assay, inhibited corneal fibroblast-induced collagen lattice contraction, and reduced MMP-2 and MMP-9 secretion into the supernatant of cell cultures in a dose-dependent manner. The expression of fibronectin was significantly decreased, while the expression of collagen I was only decreased when treated with 10 μm pioglitazone. Cell viability was not evidently changed compared to the control. CONCLUSION: This in vitro study demonstrated the anti-fibrotic effect of pioglitazone, suggesting that activation of PPARγ may be a new approach for the treatment of corneal opacity and scar formation in the corneal wound healing process. Molecular Vision 2009-11-10 /pmc/articles/PMC2776343/ /pubmed/19936025 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Pan, Hongwei Chen, Jiansu Xu, Jintang Chen, Miaojiao Ma, Rong Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts |
title | Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts |
title_full | Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts |
title_fullStr | Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts |
title_full_unstemmed | Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts |
title_short | Antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts |
title_sort | antifibrotic effect by activation of peroxisome proliferator-activated receptor–γ in corneal fibroblasts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776343/ https://www.ncbi.nlm.nih.gov/pubmed/19936025 |
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