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。

基本信息

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

项目摘要

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.

环孢霉素A（CSA）是一种免疫磷酸盐剂，通过减少成纤维细胞减少胶原蛋白吞噬作用而诱导纤维牙龈过度生长。不同的受体参与胶原蛋白吞噬作用中胶原蛋白与成纤维细胞的结合，而α2β1整联蛋白是成纤维细胞上I型胶原蛋白的特定受体。为了阐明A2F3L整联蛋白在CSA诱导的牙龈过度生长中的作用，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。纤维细胞是从含有或缺乏CSA的大鼠饮食中的30天的大鼠牙龈中分离出来的。进行了流式细胞仪分析，以测量成纤维细胞中的胶原蛋白吞噬作用和CT2整联蛋白表达。此外，从成纤维细胞中分离总RNA，并进行了逆转录酶 - 聚合酶链反应以研究CX2整合素的mRNA水平。进行了和cDNA微阵列，以检查CSA处理的和对照大鼠牙龈蛋白体外胶原蛋白吞噬作用测定中的各种RNA表达式表明，CSA处理的和对照成纤维细胞的平均值分别为13.5％和36.1％吞噬细胞。 CSA处理的成纤维细胞的β1整联蛋白表达低28％，而CSA处理的成纤维细胞中α2整合素的mRNA表达显然低于对照组中的mRNA，但F31整合素的mRNA表达不受影响。 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 gingiva may be inhibited of collagen phagocytosis by reducing cc2 integrin expression Through the inhibition牙龈成纤维细胞中的C-Fos mRNA。