RRC ID 68691
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
Abstract 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.
Volume 53(4)
Pages 1846-51
Published 2012-4-6
DOI 10.1167/iovs.11-8380
PII iovs.11-8380
PMID 22410565
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
IF 3.47
Human and Animal Cells SRA 01/04(RCB1591)