Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth: A study with cathepsin-L-deficient micey

Fusanori Nishimura, Hisa Naruishi, Koji Naruishi, Teruo Yamada, Junzo Sasaki, Christoph Peters, Yasuo Uchiyama, Yoji Murayama

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2047-2052
Number of pages6
JournalAmerican Journal of Pathology
Volume161
Issue number6
DOIs
Publication statusPublished - Dec 1 2002
Externally publishedYes

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Gingival Overgrowth
Mucolipidoses
Cathepsin L
Pharmaceutical Preparations
Cathepsin B
Gingiva
Calcium
Skin Abnormalities
Lysosomal Storage Diseases
Thapsigargin
Uridine Diphosphate
Glucosamine
Nifedipine
Fibroblasts
Observation
Hypertension
Phenotype
Messenger RNA
Skin

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth : A study with cathepsin-L-deficient micey. / Nishimura, Fusanori; Naruishi, Hisa; Naruishi, Koji; Yamada, Teruo; Sasaki, Junzo; Peters, Christoph; Uchiyama, Yasuo; Murayama, Yoji.

In: American Journal of Pathology, Vol. 161, No. 6, 01.12.2002, p. 2047-2052.

Research output: Contribution to journalArticle

Nishimura, Fusanori ; Naruishi, Hisa ; Naruishi, Koji ; Yamada, Teruo ; Sasaki, Junzo ; Peters, Christoph ; Uchiyama, Yasuo ; Murayama, Yoji. / Cathepsin-L, a key molecule in the pathogenesis of drug-induced and I-cell disease-mediated gingival overgrowth : A study with cathepsin-L-deficient micey. In: American Journal of Pathology. 2002 ; Vol. 161, No. 6. pp. 2047-2052.
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