Study of AP-1 in cyclosporine A-induced gingival overgrowth in rats.

AP-1在环孢素A诱导的大鼠牙龈过度生长中的研究。

• 批准号: 14571983
• 负责人: KATAOKA Masatoshi
• 金额: $ 1.92万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571983/
• 关键词: Cyclosporine A; Drug-induced gingival overgrowth; α2 integrin; Collagen phagocytosis; AP-1; Fibroblast; アルファ2インテグリン; 歯肉増殖症

Cyclosporine A (CsA), an immunosuppresive agent, induces fibrous gingival overgrowth through reduction of collagen phagocytosis by fibroblasts. Distinct receptors are involved in the binding of collagen to fibroblasts in collagen phagocytosis, and α2β1 integrin serves as a specific receptor for type I collagen on fibroblasts. To elucidate the role ofa2f3l integrin in CsA-induced gingival overgrowth, we investigated collagen phagocytosis and α2β1 integrin expression in rat gingival overgrowth.Fibroblasts were isolated from gingiva of rats fed a powdered diet containing or lacking CsA for 30 days. Flow cytometric analysis were performed to measure the collagen phagocytosis and the ct2 integrin expression in fibroblasts. Furthermore, total RNAs were isolated from fibroblasts, and the reverse transcriptase-polymerase chain reaction was employed to investigate the mRNA levels of cx2 integrin. And cDNA microarrays were performed to examine the various RNA expressions in CsA-treated and control rat gingivalIn vitro collagen phagocytosis assay revealed that CsA-treated and control fibroblasts contained a mean of 13.5% and 36.1% phagocytic cells, respectively. CsA-treated fibroblasts had 28% lower expression of β1 integrin than that of control, and mRNA expression of α2 integrin in CsA-treated fibroblasts was apparently lower than in the controls, but the mRNA expression of f31 integrin was not affected. Furthermore, mRNA expression of c-fos in CsA-treated rat gingiva, a subunit of AP-1, which binds to enhancer region of a2 integrin and up-regulates of it expression, was suppressed to 49% of control rat gingiva.These findings suggest that one etiological factor of gingival overgrowth may be inhibition of collagen phagocytosis by reducing cc2 integrin expression through the inhibition of c-fos mRNA in gingival fibroblasts.

环孢素 A (CsA) 是一种免疫抑制剂，通过减少成纤维细胞对胶原蛋白的吞噬作用来诱导纤维性牙龈过度生长。在胶原蛋白吞噬作用中，不同的受体参与胶原蛋白与成纤维细胞的结合，α2β1 整合素是 I 型胶原蛋白的特异性受体。阐明a2f3l整合素的作用。在CsA诱导的牙龈过度生长中，我们研究了大鼠牙龈过度生长中的胶原蛋白吞噬作用和α2β1整合素表达。从喂食含有或缺乏CsA的粉状饮食30天的大鼠的牙龈中分离成纤维细胞，进行流式细胞术分析以测量胶原蛋白吞噬作用和α2β1整合素表达。成纤维细胞中的ct2整合素表达此外，从成纤维细胞中分离出总RNA，并且采用逆转录酶-聚合酶链式反应检测cx2整合素的mRNA水平，并用cDNA微阵列检测CsA处理和对照大鼠牙龈中的各种RNA表达。体外胶原吞噬实验显示CsA处理和对照成纤维细胞含有。吞噬细胞的平均值分别为 13.5% 和 36.1%。 CsA处理的成纤维细胞中β1整合素的表达量比对照组低28%，α2整合素的mRNA表达量明显低于对照组，但f31整合素的mRNA表达量不受影响，此外，c-fos的mRNA表达量不受影响。在 CsA 处理的大鼠牙龈中，与 a2 整合素增强子区域结合并上调其表达的 AP-1 亚基受到抑制对照大鼠牙龈的 49%。这些发现表明，牙龈过度生长的病因之一可能是通过抑制牙龈成纤维细胞中的 c-fos mRNA 来减少 cc2 整合素表达，从而抑制胶原蛋白吞噬作用。

项目成果

Yamashita K, Ichikawa T, Yamamoto T, Kataoka M, Nakagawa Y, Terada H, Shinohara Y.: "Three-way effect of cyanine dye on the structure and function of mitochondria."J Health Sci. 49. 448-453 (2003)

Yamashita K、Ichikawa T、Yamamoto T、Kataoka M、Nakakawa Y、Terada H、Shinohara Y.：“花青染料对线粒体结构和功能的三向效应。”J Health Sci。

Shimisu Y, Kataoka M, Seto H, Kido J, Ngara T: "Nifedipine induces gingival epithelial hyperplasia in rats through inhibition of apoptosis."J Peridontol. 73. 861-867 (2002)

Shimisu Y、Kataoka M、Seto H、Kido J、Ngara T：“硝苯地平通过抑制细胞凋亡诱导大鼠牙龈上皮增生。”J Peridontol。

Kido J, Kido R, Suryono, Kataoka M, Nagata T: "Calprotectin release from human neutrophils is induced by Poryromonas gingivalis lipopolysaccharide via the CD-14-Toll-like receptor-nuclear factor kappa B pathway."J Periodont Res. 38. 557-563 (2003)

Kido J、Kido R、Suyono、Kataoka M、Nagata T：“牙龈卟啉单胞菌脂多糖通过 CD-14-Toll 样受体-核因子 kappa B 途径诱导人中性粒细胞释放钙卫蛋白。”J periodont Res。

Suryono, Kido J, Hayashi N, Kataoka M, Nagata T: "Effects of Porphyromonas gingivalis lipopolysaccharide, tumor necrosis factor, and interleukin 1-beta on calprotectin release in human monocytes."J Periodontol. 74. 1719-1724 (2003)

Suryono、Kido J、Hayashi N、Kataoka M、Nagata T：“牙龈卟啉单胞菌脂多糖、肿瘤坏死因子和白细胞介素 1-β 对人类单核细胞钙卫蛋白释放的影响。”J periodontol。

Kajimoto K, Daikoku T, Kita F, Yamazaki N, Kataoka M et al.: "PCR-select subtraction for characterization of messages differentially expressed in brown compared with white adipose tissue"Mol Genet Metab. 80. 255-261 (2003)

Kajimoto K、Daikoku T、Kita F、Yamazaki N、Kataoka M 等人：“PCR 选择扣除法用于表征棕色脂肪组织与白色脂肪组织中差异表达的信息”Mol Genet Metab。