Tranilast inhibits TGF-β-induced collagen gel contraction mediated by human corneal fibroblasts  

作　　者：Ye Liu Xiao-Jing Zhao Xiao-Shuo Zheng Hui Zheng Lei Liu Ling-Bin Meng Qin Li Yang Liu 

机构地区：[1]Department of Pathology,the Fifth Affiliated Hospital,Sun Yat-sen University [2]Department of Ophthalmology,the Fifth Affiliated Hospital,Sun Yat-sen University [3]Department of Ophthalmology,the First Hospital of Jilin University [4]Department of Internal Medicine,Florida Hospital

出　　处：《International Journal of Ophthalmology(English edition)》2018年第8期1247-1252,共6页国际眼科杂志（英文版）

基　　金：Supported by the National Science Foundation of China (No.81770889);the Natural Science Foundation of Guangdong Province (No.2017A030313774);the Research Fund of Jilin Provincial Science and Technology Department to Yang Liu (International Cooperation Item, No.20160414055GH)

摘　　要：AIM： To determine if tranilast affects human corneal fibroblast（HCFs） contraction.METHODS： HCFs cultured in a three-dimensional type I collagen gel were treated with or without transforming growth factor beta（TGF-β） or tranilast. Gel diameter was measured as an indicator for collagen contraction. Immunoblot was performed to evaluate myosin light chain（MLC） and paxillin phosphorylation. Confocal microscopy was employed to examine the focal adhesions and actin stress fiber formation. Immunoblot analysis and gelatin zymography were performed to detect tissue inhibitors of metalloproteinases and matrix metalloproteinases（MMPs） in supernatant.RESULTS： The inhibitory effect of tranilast on HCFsmediated collagen gel contraction induced by TGF-β was dose-dependent. The significant effect of tranilast was started from 100 μmol/L and maximized at 300 μmol/L. The peak effect of 300 μmol/L tranilast also relied on the duration of treatment, which showed statistical significance from day 2. TGF-β-induced paxillin and MLC phosphorylation, stress fiber formation, focal adhesions, and MMP-1, MMP-2, and MMP-3 secretion in HCFs were also inhibited by tranilast.CONCLUSION： Tranilast suppresses the HCFs-cultured collagen gel contraction induced by TGF-β. It attenuates actin stress fibers formation, focal adhesions, and the secretion of MMPs, with these actions likely contributing to the inhibitory effect on HCF contractility. By attenuating the contractility of corneal fibroblasts, tranilast treatment may inhibit corneal scarring.AIM： To determine if tranilast affects human corneal fibroblast（HCFs） contraction.METHODS： HCFs cultured in a three-dimensional type I collagen gel were treated with or without transforming growth factor beta（TGF-β） or tranilast. Gel diameter was measured as an indicator for collagen contraction. Immunoblot was performed to evaluate myosin light chain（MLC） and paxillin phosphorylation. Confocal microscopy was employed to examine the focal adhesions and actin stress fiber formation. Immunoblot analysis and gelatin zymography were performed to detect tissue inhibitors of metalloproteinases and matrix metalloproteinases（MMPs） in supernatant.RESULTS： The inhibitory effect of tranilast on HCFsmediated collagen gel contraction induced by TGF-β was dose-dependent. The significant effect of tranilast was started from 100 μmol/L and maximized at 300 μmol/L. The peak effect of 300 μmol/L tranilast also relied on the duration of treatment, which showed statistical significance from day 2. TGF-β-induced paxillin and MLC phosphorylation, stress fiber formation, focal adhesions, and MMP-1, MMP-2, and MMP-3 secretion in HCFs were also inhibited by tranilast.CONCLUSION： Tranilast suppresses the HCFs-cultured collagen gel contraction induced by TGF-β. It attenuates actin stress fibers formation, focal adhesions, and the secretion of MMPs, with these actions likely contributing to the inhibitory effect on HCF contractility. By attenuating the contractility of corneal fibroblasts, tranilast treatment may inhibit corneal scarring.

关 键 词：TRANILAST transforming growth factor beta corneal fibroblast corneal wound healing 

分 类 号：TF3[冶金工程—冶金机械及自动化]