Gene Therapy for Periodontal Diseases -Regulation of host response by local gene delivery-

牙周病基因治疗 -通过局部基因传递调节宿主反应 -

基本信息

批准号：
14370710
负责人：
TAKASHIBA Shogo
金额：
$ 8.64万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

Because understanding the target factor was important, we decided to specify the target factor from both sides of non-specific host defense and tissue regeneration. Moreover, because it was also anxiety against clinical application of gene therapy because of its toxicity, the experiments are performed for testing it.1.Target geneIn the rat, cytochrome c oxidase gene expressed strongly at 1 week and pro-α-2 type I collagen gene expressed strongly at 2.5 weeks after alveolar bone begun regeneration. Activation of these genes seem to be needed for alveolar bone regeneration. In dental pulp would, the homolong of human 12.7K-interacting protein 2 expressed strongly. We named it rat FIP-2 gene. It is under analyzing now for physiological meaning. In addition, inflammation, promoter region required for LPS-induced transcription of LITAF was revealed, which is new transcription factor for human tumor necrosis factor(TNF)-α.2.Introduction of β-defensin by non-viral vectorAnti-bacterium peptide β-defensin gene was transferred to human epithelial cells and rat salivary glands to test its effect for reduce bacteria around cultured cells or rat oral cavity. Furthermore, its effect for local tissue inflammation was also examined. We found that bacterial numbers are reduced and that no obvious inflammation in rat salivary gland tissue. However, when electroporation was used for gene delivery, obvious inflammation was detected. Furthermore, It was revealed that β-defensin gene transcription requires 2 regions of NF-kB binding domain on its promoter, but that NF-IL6 biding domain on it acts to reduce its transcription.

由于了解目标因素很重要，因此我们决定指定非特异性宿主防御和组织再生两侧的目标因素。此外，由于由于其毒性而对基因疗法的临床应用也是焦虑，因此进行了实验以测试它。1.TargetGenein the the Rat，细胞色素C氧化酶基因基因在1周时强烈表达，Pro-α-2型I型胶原蛋白胶原蛋白基因在肺泡骨开始后的2.5周表示强烈表达。这些基因的激活似乎需要用于全动骨骨再生。在牙纸浆中，人类的12.7k相互作用蛋白2的同龙强烈表达。我们将其命名为大鼠FIP-2基因。现在正在分析它的物理意义。此外，揭示了炎症，LPS诱导的LITAF转录所需的启动子区域，这是人类肿瘤坏死因子（TNF）-α.2。非病毒viral载体 - viraTANI-BACTERATIM-BACTERIM-BACTERIM-BACTERIM-BACTERIM-BACTERIUM-BACTERIUM-BACTERIUM肽β-反触细胞素围绕人类表皮细胞的作用，这是对β-防御素的研究的新转录因子。细胞或大鼠口腔。此外，还检查了其对局部组织感染的影响。我们发现细菌数量减少，并且大鼠唾液腺组织中没有明显的炎症。但是，当将电穿孔用于基因输送时，明显的炎症此外，据表明，β-防御素基因转录需要在其启动子上的NF-KB结合域的2个区域，但是NF-IL6竞标域对其进行了减少转录。