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The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy

Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM) is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR) δ had antifibrosis effects in...

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Autores principales: Gu, Yun, Li, Xuan, He, Tiangeng, Jiang, Zhixin, Hao, Peng, Tang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248330/
https://www.ncbi.nlm.nih.gov/pubmed/25477952
http://dx.doi.org/10.1155/2014/464935
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author Gu, Yun
Li, Xuan
He, Tiangeng
Jiang, Zhixin
Hao, Peng
Tang, Xin
author_facet Gu, Yun
Li, Xuan
He, Tiangeng
Jiang, Zhixin
Hao, Peng
Tang, Xin
author_sort Gu, Yun
collection PubMed
description Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM) is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR) δ had antifibrosis effects in a rat model of corneal damage. Adult Sprague-Dawley rats underwent bilateral phototherapeutic keratectomy (PTK). The eyes were randomized into four groups: PBS, GW501516 (a selective agonist of PPARδ), GSK3787 (a selective antagonist of PPARδ), or GW501516 combined with GSK3787. The agents were subconjunctivally administered twice a week until sacrifice. The cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and postmortem histology. A myofibroblast marker (α-smooth muscle actin) and ECM production (fibronectin, collagen type III and collagen type I) were examined by immunohistochemistry and RT-PCR. At the early stages of wound healing, GW501516 inhibited reepithelialization and promoted angiogenesis. During the remodeling phase of wound healing, GW501516 attenuated the activation and proliferation of keratocytes, which could be reversed by GSK3787. GW501516 decreased transdifferentiation from keratocytes into myofibroblasts, ECM synthesis, and corneal haze. These results demonstrate that GW501516 controls corneal fibrosis and suggest that PPARδ may potentially serve as a therapeutic target for treating corneal scars.
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spelling pubmed-42483302014-12-04 The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy Gu, Yun Li, Xuan He, Tiangeng Jiang, Zhixin Hao, Peng Tang, Xin PPAR Res Research Article Corneal stromal fibrosis characterized by myofibroblasts and abnormal extracellular matrix (ECM) is usually the result of inappropriate wound healing. The present study tested the hypothesis that the ligand activation of peroxisome proliferator-activated receptor (PPAR) δ had antifibrosis effects in a rat model of corneal damage. Adult Sprague-Dawley rats underwent bilateral phototherapeutic keratectomy (PTK). The eyes were randomized into four groups: PBS, GW501516 (a selective agonist of PPARδ), GSK3787 (a selective antagonist of PPARδ), or GW501516 combined with GSK3787. The agents were subconjunctivally administered twice a week until sacrifice. The cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and postmortem histology. A myofibroblast marker (α-smooth muscle actin) and ECM production (fibronectin, collagen type III and collagen type I) were examined by immunohistochemistry and RT-PCR. At the early stages of wound healing, GW501516 inhibited reepithelialization and promoted angiogenesis. During the remodeling phase of wound healing, GW501516 attenuated the activation and proliferation of keratocytes, which could be reversed by GSK3787. GW501516 decreased transdifferentiation from keratocytes into myofibroblasts, ECM synthesis, and corneal haze. These results demonstrate that GW501516 controls corneal fibrosis and suggest that PPARδ may potentially serve as a therapeutic target for treating corneal scars. Hindawi Publishing Corporation 2014 2014-11-13 /pmc/articles/PMC4248330/ /pubmed/25477952 http://dx.doi.org/10.1155/2014/464935 Text en Copyright © 2014 Yun Gu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under 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
Gu, Yun
Li, Xuan
He, Tiangeng
Jiang, Zhixin
Hao, Peng
Tang, Xin
The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy
title The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy
title_full The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy
title_fullStr The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy
title_full_unstemmed The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy
title_short The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptor δ on Rat Corneal Wound Healing after Excimer Laser Keratectomy
title_sort antifibrosis effects of peroxisome proliferator-activated receptor δ on rat corneal wound healing after excimer laser keratectomy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248330/
https://www.ncbi.nlm.nih.gov/pubmed/25477952
http://dx.doi.org/10.1155/2014/464935
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