Reference - Detail
|Author||Hori K, Matsuda A, Ebihara N, Imai K, Mori K, Funaki T, Watanabe Y, Nakatani S, Okada K, Matsuo O, Murakami A.|
|Title||Involvement of plasminogen activator inhibitor-1 in the pathogenesis of atopic cataracts.|
|Journal||Invest Ophthalmol Vis Sci|
PURPOSE:Further to our previous report of a genetic association between interferon-gamma (IFN-γ) receptor 1 gene and atopic cataract, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1), a fibrosis-related, IFN-γ downstream molecule, in the pathogenesis of atopic cataracts.
METHODS:Cultured lens epithelial cells (LECs) were stimulated by IFN-γ and quantified by PAI-1 mRNA/protein expression. PAI-1 and TGF-β mRNA expression was quantified using cDNA samples obtained from the lens epithelium of atopic cataract patients (n = 7) and of senile cataract patients (n = 8). The anterior capsules obtained from atopic cataracts (n = 9) were immunostained with anti-PAI-1 and anti-alpha smooth muscle actin (α-SMA) antibodies. PAI-1 gene expression was knocked down by PAI-1 siRNA, and α-SMA expression was examined under TGF-β1 stimulation. Expression of α-SMA was examined as a pathological hallmark of anterior subcapsular cataracts, commonly observed in atopic cataracts.
RESULTS:The IFN-γ stimulation induced PAI-1 mRNA/protein expression in the LECs from 24 to 48 hours after stimulation. The expression of PAI-1 mRNA and TGF-β1 mRNA was significantly higher in the cDNA samples obtained from the atopic cataracts than those obtained from the senile cataracts. PAI-1-positive immunostaining was observed at the fibrotic lesion of the atopic cataracts, and α-SMA-positive myofibroblasts were observed at the vicinity of the PAI-1-positive lesion in all nine samples examined. PAI-1 gene knockdown resulted in reduced α-SMA expression in the LECs.
CONCLUSIONS:The findings of this study suggest that the IFN-γ, PAI-1, and TGF-β1 are involved in the pathophysiology of atopic cataracts.
|MeSH||Blotting, Western Cataract / genetics* Cataract / metabolism Cataract / pathology Cells, Cultured Epithelial Cells / drug effects Epithelial Cells / metabolism Epithelial Cells / ultrastructure Gene Expression Regulation* Humans Immunohistochemistry Interferon-gamma / pharmacology Lens, Crystalline / drug effects Lens, Crystalline / metabolism* Lens, Crystalline / pathology Microscopy, Electron Plasminogen Activator Inhibitor 1 / biosynthesis Plasminogen Activator Inhibitor 1 / genetics RNA, Messenger / genetics* Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta1 / biosynthesis Transforming Growth Factor beta1 / genetics|
|Human and Animal Cells||SRA 01/04(RCB1591)|