IL 1 REGULATION OF MMP GENES IN GINGIVAL FIBROBLASTS

IL 1 对牙龈成纤维细胞中 MMP 基因的调节

• 批准号: 6176133
• 负责人: RUTH C BORGHAEI
• 金额: $ 9.99万
• 依托单位: PHILADELPHIA COLLEGE OF OSTEOPATHIC MED
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176133
• 关键词: DNA footprinting; SDS polyacrylamide gel electrophoresis; collagenase; fibroblasts; gene expression; genetic promoter element; genetic regulation; genetic transcription; gingiva; human tissue; interleukin 1; metalloendopeptidases; molecular cloning; periodontitis; polymerase chain reaction; stromelysin; tissue /cell culture; transcription factor; transfection

DESCRIPTION (Adapted from investigator's Abstract): Interleukin-1 (IL-1) stimulates production of metalloproteinases (MMPs, e.g. collagenase and stromelysin) by gingival fibroblasts, and has therefore been linked to soft tissue destruction associated with periodontitis. Although the precise mechanisms of IL-1 induction of MMP gene transcription have not been fully elucidated, evidence suggests that the effects of IL-1 are mediated by multiple transcription factors which may interact with the promoters in complex and cell specific ways. The specific aims of this proposal are: 1) to identify transcription factors that specifically interact with the promoter regions of collagenase and stromelysin genes following IL-1 stimulation of gingival fibroblasts; 2) to determine the role(s) of factors identified in Specific Aim 1 in regulating transcription of collagenase and/or stromelysin genes in response to IL-1; and, 3) to further characterize, and clone or purify, any previously unknown factor(s) identified in Specific Aim 1 and shown to play a significant role in the regulation of MMP genes. These specific aims will be accomplished through the use of DNAse footprinting/methylation interference and transient transfection experiments to systematically dissect the promoters in search of regulatory elements and binding complexes. In addition to providing important new information about how production of MMPs is regulated, these studies might also identify new potential targets for therapeutic agents for periodontitis.

描述（根据研究者的摘要进行了改编）：白介素-1（IL-1） 刺激金属蛋白酶的产生（MMP，例如胶原酶和 通过牙龈成纤维细胞，Stromelysin），因此已与柔软链接 与牙周炎有关的组织破坏。 虽然是确切的 MMP基因转录的IL-1诱导机制尚未完全 阐明的证据表明，IL-1的作用是由 可能与启动子相互作用的多个转录因子 复杂和细胞特定的方式。 该提议的具体目的是：1） 确定特异性相互作用的转录因子 IL-1之后的胶原酶和Stromelysin基因的启动子区域 刺激牙龈成纤维细胞； 2）确定因素的作用 在调节胶原酶转录时在特定目标1中识别 响应IL-1的基因和/或Stromelysin基因； 3）进一步 表征，克隆或纯化，任何以前未知因素 在特定目标1中确定，并在 MMP基因的调节。 这些具体目标将通过 使用DNase足迹/甲基化干扰和瞬态 转染实验系统地剖析启动子搜索 调节元件和结合复合物的。 除了提供 有关如何调节MMP的生产的重要新信息， 研究还可能确定治疗剂的新潜在靶标 牙周炎。