Transcriptional regulation of amelotin gene by proinflammatory cytokines in gingival fibroblasts

Transcriptional regulation of amelotin gene by proinflammatory cytokines in gingival fibroblasts
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DOI:
10.3109/03008207.2014.923848
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发表时间:
2014-08-01
影响因子:
2.9
通讯作者:
Ogata, Yorimasa
Ogata, Yorimasa
中科院分区:
医学3区
文献类型:
--
作者:
Nakayama, Yohei;Takai, Hideki;Ogata, Yorimasa

文献摘要

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Amelotin(AMTN)是在釉质形成的晚期和在结合上皮中表达的分泌蛋白。在众多的差异表达基因中,我们通过基因芯片技术发现AMTN mRNA在炎症牙龈组织中的表达显著增加。实时荧光定量聚合酶链反应证实了AMTN mRNA在炎症牙龈和人牙龈成纤维细胞(HGF)中的表达。为了确定AMTN表达的分子基础及其受促炎细胞因子的调节,我们分离并鉴定了小鼠AMTN基因的启动子区。使用包括小鼠AMTN基因启动子的荧光素酶构建体进行瞬时转染测定。白细胞介素-1 β、白细胞介素-6和肿瘤坏死因子-α诱导HGF中AMTN mRNA水平。这些细胞因子增加AMTN启动子构建体在HGF中的荧光素酶活性。结果表明,促炎细胞因子诱导AMTN基因转录和AMTN在牙龈炎症中的作用。
Amelotin (AMTN) is a secreted protein expressed during the late stages of enamel formation and in the junctional epithelium. Among many differentially expressed genes, we found significantly increased AMTN mRNA level in inflamed gingiva by DNA microarray. The inductions of AMTN mRNA expressions in inflamed gingiva and human gingival fibroblasts (HGF) were confirmed by real-time polymerase chain reaction. To determine the molecular basis of the expression of AMTN and its regulation by proinflammatory cytokines, we have isolated and characterized the promoter region of mouse AMTN gene. Transient transfection assays were performed using luciferase constructs including mouse AMTN gene promoter. Interleukin-1 beta, Interleukin-6 and tumor necrosis factor-a induced AMTN mRNA levels in HGF. These cytokines increased the luciferase activities of the AMTN promoter constructs in HGF. The results suggest that proinflammatory cytokines induce AMTN gene transcription and a role for AMTN in gingival inflammation.