論文 - 詳細
| RRC ID | 6022 |
|---|---|
| 著者 | Nishimura F, Naruishi H, Naruishi K, Yamada T, Sasaki J, Peters C, Uchiyama Y, Murayama Y. |
| タイトル | Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth: a study with cathepsin-L-deficient mice. |
| ジャーナル | Am J Pathol |
| Abstract |
Drug-induced gingival overgrowth, the chronic side effect of calcium antagonists, is frequently seen due to the increase in patients with hypertension, although the etiology of the disease is largely unknown. I-cell disease, which accompanies gingival overgrowth, is characterized by a deficiency in UDP-N-acetyl-glucosamine and is classified as one of the lysosomal storage diseases. Here, we hypothesized that a common mechanism may underlie the etiology of gingival overgrowth seen in patients treated with calcium antagonist and in patients with I-cell disease. A calcium antagonist, nifedipine, specifically suppressed cathepsin-L activity and mRNA expression, but not that of cathepsin-B in cultured gingival fibroblasts. The activity of cathepsin-L was suppressed up to 50% at 24 hours after treatment of the cells with the reagent. The selective suppression of cathepsin-L activity appeared not to be dependent on Ca(2+), since treatment of the cells with thapsigargin suppressed both cathepsin-B and -L activity. Mice deficient in the cathepsin-L gene manifested enlarged gingivae. Histological observation of the gingivae demonstrated typical features of acanthosis, a phenotype very similar to that of experimentally induced gingival overgrowth. Since cathepsin-L deficiency was reported to be associated with thickening of the skin, impaired cathepsin-L activity may play a key role in the establishment of skin and gingival abnormalities seen in I-cell disease. In addition, reduced cathepsin-L activity may play an important role in inducing drug-induced gingival overgrowth. |
| 巻・号 | 161(6) |
| ページ | 2047-52 |
| 公開日 | 2002-12-1 |
| DOI | 10.1016/S0002-9440(10)64483-5 |
| PII | S0002-9440(10)64483-5 |
| PMID | 12466121 |
| PMC | PMC1850915 |
| MeSH | Animals Calcium / metabolism Calcium Channel Blockers / pharmacology Cathepsin B / genetics Cathepsin B / metabolism Cathepsin L Cathepsins / genetics Cathepsins / metabolism* Cells, Cultured Cysteine Endopeptidases / metabolism* Enzyme Inhibitors / pharmacology Fibroblasts / cytology Fibroblasts / drug effects Gingiva / cytology Gingiva / metabolism Gingiva / pathology Gingival Overgrowth / chemically induced Gingival Overgrowth / etiology* Gingival Overgrowth / metabolism* HeLa Cells Humans Lysosomes / enzymology Mice Mice, Knockout Mucolipidoses / complications Mucolipidoses / metabolism* Mucolipidoses / physiopathology Nifedipine / pharmacology Thapsigargin / pharmacology |
| IF | 3.491 |
| 引用数 | 24 |
| WOS 分野 | PATHOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00806 |