Lipopolysaccharide induces a stromal-epithelial signalling axis in a rat model of chronic periodontitis
Lipopolysaccharide induces a stromal-epithelial signalling axis in a rat model of chronic periodontitis
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DOI：
10.1111/jcpe.12023
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发表时间：
2013-01-01
影响因子：
6.7
通讯作者：
Putnins, Edward E.
中科院分区：
文献类型：
--
作者：
Firth, James D.;Ekuni, Daisuke;Putnins, Edward E.
目的 脂多糖是一种与慢性牙周炎有关的细菌毒力因子，它可能穿透交界上皮屏障和基底膜，损害下面的基质。我们试图确定脂多糖诱导的全局基因表达变化，这些变化负责疾病发作期间间质和上皮之间的信号传导。材料和方法使用大鼠脂多糖牙周炎模型，通过激光捕获显微切割从健康和患病动物中分别收集交界上皮和底层基质组织，并进行基因表达微阵列分析。确定的关键基因产物在牙龈上皮细胞和成纤维细胞培养物中得到验证。结果在两种组织类型中和之间发现了区分健康与疾病的全局基因表达模式。在基质中，改变最显着的基因本体功能组（Z >= 4.00）是细胞因子，包含最显着（+/- 2 倍；p < 0.05）上调的基因双调蛋白、IL1-β 和 Fas 配体，它们都是上皮生长因子受体途径的阳性、可扩散调节剂。在上皮细胞中，最显着的变化是下调的 FOS 相关抗原 1 基因、生长抑素受体 2 基因和粘蛋白 4 基因，它们都是上皮生长因子受体途径的负调节剂。结论这些结果建立了用于研究基因产物相互作用的牙周炎模型，并表明交界上皮疾病过度增殖的发生涉及协调的基质上皮信号传导轴。
Aim Lipopolysaccharide is a bacterial virulence factor implicated in chronic periodontitis, which may penetrate the junctional epithelial barrier and basement membrane to insult underlying stroma. We sought to identify lipopolysaccharide-induced global gene expression changes responsible for signalling between stroma and epithelium during disease onset.Materials and Methods Using a rat lipopolysaccharide periodontitis model, junctional epithelium and underlying stromal tissue were separately collected from healthy and diseased animals by laser-capture microdissection and subject to gene expression microarray analysis. Key gene products identified were validated in gingival epithelial and fibroblast cell cultures.Results Global gene expression patterns distinguishing health versus disease were found in and between both tissue types. In stroma, the most significantly altered gene ontology function group (Z >= 4.00) was cytokines, containing most significantly (+/- 2-fold; p < 0.05) upregulated genes amphiregulin, IL1-beta and Fas ligand, all positive, diffusible modulators of the epithelial growth factor receptor pathway. In epithelium, the most significant changes were in downregulated FOS-related antigen-1 gene, somatostatin receptor-2 gene and mucin-4 gene, all negative modulators of the epithelial growth factor receptor pathway.Conclusion These results establish a periodontitis model for studying gene product interactions and suggests that the onset of junctional epithelial disease hyperproliferation involves a concerted stromalepithelial signalling axis.