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Inhibitory Effect of Tranilast on Transforming Growth Factor-Beta-Induced Protein in Granular Corneal Dystrophy Type 2 Corneal Fibroblasts

 Kim, Tae-im  ;  Lee, Hun  ;  Hong, Hye Kyoung  ;  Kim, Kyu Seo  ;  Choi, Seung-Il  ;  Maeng, Yong-Sun  ;  Kim, Eung Kweon 
 CORNEA, Vol.34(8) : 950-958, 2015 
Journal Title
Issue Date
Actins/metabolism ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology* ; Blotting, Western ; Cell Proliferation/drug effects ; Cells, Cultured ; Collagen Type I/metabolism ; Corneal Dystrophies, Hereditary/drug therapy* ; Corneal Dystrophies, Hereditary/genetics ; Corneal Dystrophies, Hereditary/metabolism ; Corneal Keratocytes/drug effects* ; Corneal Keratocytes/metabolism ; Extracellular Matrix Proteins/genetics* ; Extracellular Matrix Proteins/metabolism* ; Fluorescent Antibody Technique, Indirect ; Humans ; Integrins/metabolism ; Microscopy, Confocal ; Phosphorylation ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Smad2 Protein/metabolism ; Smad3 Protein/metabolism ; Transforming Growth Factor beta/genetics* ; Transforming Growth Factor beta/metabolism* ; Transforming Growth Factor beta/pharmacology ; Wound Healing/drug effects ; Wound Healing/physiology ; ortho-Aminobenzoates/pharmacology*
tranilast ; TGFBIp ; TGF-β ; pSmad ; α-SMA ; corneal dystrophy
PURPOSE: To investigate the effects of tranilast, an inhibitor of chemical mediators and fibroblast proliferation, on the expression of transforming growth factor-beta (TGF-β)-induced protein (TGFBIp) in wild-type (WT) and homozygous (HO) granular corneal dystrophy type 2 corneal fibroblasts. METHODS: Cell proliferation and cytotoxicity were measured by Cell Counting Kit-8 and lactate dehydrogenase assay. Western blotting and real-time polymerase chain reaction were used to determine changes in the expression of TGFBIp and TGFBI mRNA. We determined the effects of tranilast on phosphorylated Smad2 (pSmad2) and pSmad3, wound-healing, and expression of alpha-smooth muscle actin (α-SMA), type I collagen, and integrins. RESULTS: High concentrations of tranilast decreased proliferation of corneal fibroblasts but did not cause elevation of lactate dehydrogenase, except at 1.0 mM tranilast. TGF-β increased the expression of TGFBIp and TGFBI mRNA in WT and HO corneal fibroblasts. Cotreatment of corneal fibroblasts with tranilast and TGF-β reduced the levels of TGFBIp and TGFBI mRNA. In addition, application of tranilast reduced pSmad2 in WT and HO corneal fibroblasts and pSmad3 in HO corneal fibroblasts, both of which were increased initially by TGF-β. Tranilast delayed wound healing and reduced the expression of α-SMA, type I collagen, and some of integrins in WT and HO corneal fibroblasts. CONCLUSIONS: Application of tranilast in WT and HO corneal fibroblasts inhibited the expression of TGFBIp by blocking TGF-β signaling. Thus, tranilast may be useful in delaying or preventing the recurrence of corneal opacity in TGFBI-linked corneal dystrophies if clinical studies confirm these findings.
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1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Corneal Dystrophy Research Institute (각막이상증연구소) > 1. Journal Papers
Yonsei Authors
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Kim, Tae Im(김태임) ORCID logo https://orcid.org/0000-0001-6414-3842
Maeng, Yong Sun(맹용선) ORCID logo https://orcid.org/0000-0003-1694-8405
Lee, Hun(이훈)
Choi, Seung Il(최승일) ORCID logo https://orcid.org/0000-0001-7168-8795
Hong, Hye Kyoung(홍혜경)
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