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Chronic hyperglycemia reduces the expression of intercellular adhesion molecules and increases intercellular hyperpermeability in the periodontal epithelium.
Narukawa, Yuki; Sugiyama, Naoyuki; Miura, Jiro; Yamashita, Rentaro; Tominaga, Shotaro; Izumi, Yoshihiro; Bamba, Takeshi; Ishihama, Yasushi; Kashiwagi, Yoichiro; Murakami, Shinya.
Afiliación
  • Narukawa Y; Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka, Japan.
  • Sugiyama N; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
  • Miura J; Division of Interdisciplinary Dentistry, Osaka University Dental Hospital, Osaka, Japan.
  • Yamashita R; Division of Interdisciplinary Dentistry, Osaka University Dental Hospital, Osaka, Japan.
  • Tominaga S; Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka, Japan.
  • Izumi Y; Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • Bamba T; Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • Ishihama Y; Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
  • Kashiwagi Y; Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka, Japan.
  • Murakami S; Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka, Japan.
J Periodontal Res ; 58(4): 813-826, 2023 Aug.
Article en En | MEDLINE | ID: mdl-37221815
BACKGROUND/AIMS: Hyperglycemia in diabetes is closely associated with periodontal disease progression. This study aimed to investigate the effect of hyperglycemia on the barrier function of gingival epithelial cells as a cause of hyperglycemia-exacerbated periodontitis in diabetes mellitus. METHODS: The abnormal expression of adhesion molecules in gingival epithelium in diabetes was compared between db/db and control mice. To study the effects of hyperglycemia on interepithelial cell permeability, the mRNA and protein expressions of adhesion molecules were investigated using a human gingival epithelial cell line (epi 4 cells) in the presence of either 5.5 mM glucose (NG) or 30 mM glucose (HG). Immunocytochemical and histological analyses were performed. We also studied HG-related intracellular signaling to assess abnormal adhesion molecule expression in the cultured epi 4 cells. RESULTS: The results of the proteomic analysis implied the abnormal regulation of cell-cell adhesion, and mRNA and protein expression assessments revealed the significant downregulation of Claudin1 expression in the gingival tissues of db/db mice (p < .05 vs control). Similarly, the mRNA and protein expressions of adhesion molecules were lower in epi 4 cells cultured under HG conditions than in those cultured under NG conditions (p < .05). Three-dimensional culture and transmission electron microscopy revealed reduced thickness of the epithelial cell layers with no flattened apical cells and heterogeneously arranged intercellular spaces among adjacent epi 4 cells under the HG. These results were consistent with the increased permeability of epi 4 cells under the HG relative to that of cells under the NG. This abnormal expression of intercellular adhesion molecules under the HG was related to the increased expression of receptors for advanced glycation end products (AGEs) and oxidative stress relative to that seen under the NG, along with stimulation of ERK1/2 phosphorylation in epi 4 cells. CONCLUSIONS: High glucose-induced impairment of intercellular adhesion molecule expression in gingival epithelial cells was related to the intercellular permeability of gingival cells, representing a possible link to hyperglycemia-related AGE signaling, oxidative stress, and ERK1/2 activation.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Diabetes Mellitus / Hiperglucemia Límite: Animals / Humans Idioma: En Revista: J Periodontal Res Año: 2023 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Diabetes Mellitus / Hiperglucemia Límite: Animals / Humans Idioma: En Revista: J Periodontal Res Año: 2023 Tipo del documento: Article País de afiliación: Japón