論文 - 詳細
| RRC ID | 68691 |
|---|---|
| 著者 | Hori K, Matsuda A, Ebihara N, Imai K, Mori K, Funaki T, Watanabe Y, Nakatani S, Okada K, Matsuo O, Murakami A. |
| タイトル | Involvement of plasminogen activator inhibitor-1 in the pathogenesis of atopic cataracts. |
| ジャーナル | 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. |
| 巻・号 | 53(4) |
| ページ | 1846-51 |
| 公開日 | 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 |
| リソース情報 | |
| ヒト・動物細胞 | SRA 01/04(RCB1591) |