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S. Saika, K. Ikeda, O. Yamanaka, Y. Okada, T. Miyamoto, A. Kitano, Y. Ohnishi, W. W.-. Y. Kao; Effect of Overexpression of PPAR Gamma on Smad Signal in Fibroblasts and Macrophages and on the Healing Process of Corneal Alkali Burn in Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1476.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effects of adenoviral overexpression of peroxisome proliferator-activated receptor gamma (PPARg) on cell behaviors of ocular fibroblasts, macrophages and corneal epithelial cells in vitro and also to examine if topical PPARg-adenovirus (Ad) has anti-inflammatory and anti-fibrogenic effects in an alkali-burned mouse cornea.
Cultured mouse ocular fibroblasts, macrophages and SV40-immortalized corneal epithelial cell line received PPARg-Ad and were treated with TGFb1 after 48 hrs. Smad signal and fibrogenesis-related gene expression were assayed by using immunocytochemistry, western blotting or real-time RT-PCR. A mouse cornea (n = 75) burned with 1N NaOH was allowed to heal for day 5, 10 and 20 after receiving topical PPARg-Ad or control Ad. Inflammation and fibrogenic reaction in tissue were examined by using histology and immunohistochemistry. Fibrogenesis-related gene expression were assayed by using real-time RT-PCR.
PPARg overexpression suppressed expression of inflammation-related or scarring-related growth factors and matrix metalloproteinases (MMPs) in macrophages, fibroblasts and corneal epithelial cells. It also reduced expression of collagen Ia2 mRNA and fibronectin in fibroblasts. PPARg-Ad inhibited its nuclear translocation of phospho-Smad2 in the cell types in vitro. Topical PPARg-Ad suppressed up-regulation of growth factors and MMP-2, and reduced invasion of macrophages and suppressed myofibroblast generation in a healing burned cornea. Re-epihtleialization in the healing cornea was also promoted by PPARg-Ad.
Adenoviral gene transfer of PPARg has a therapeutic effect on experimental corneal alkali burn. The mechanism of action might include suppression of activation of fibroblasts and macrophages with reduction of TGFb/Smad signal.
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