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: 6379796
• 负责人: RUTH C BORGHAEI
• 金额: $ 10.49万
• 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 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379796
• 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(改编自调查人员摘要)：白细胞介素1(IL-1) 刺激金属蛋白酶(MMPs，如胶原酶和 基质分解素)通过牙龈成纤维细胞，因此与软组织有关 与牙周炎相关的组织破坏。尽管准确地说 IL-1诱导基质金属蛋白酶基因转录的机制尚未完全阐明 已阐明的证据表明，IL-1的作用是通过 可能与启动子相互作用的多种转录因子 复杂的和细胞特有的方式。这项建议的具体目的是：1) 以确定与该基因特异相互作用的转录因子 IL-1作用下胶原酶和基质分解酶基因的启动子区域 牙龈成纤维细胞的刺激作用；2)确定因子的作用(S) 在特定目的1中发现调节胶原酶转录 和/或基质分解素基因对IL-1的反应；以及，3)进一步 鉴定并克隆或纯化任何以前未知的因素(S) 在具体目标1中确定，并被证明在 基质金属蛋白酶基因的调控。这些具体目标将通过以下方式实现 利用DNA酶足迹/甲基化干扰和瞬变 系统剖析搜索中启动子的基因转染实验 调控元件和结合复合体。除了提供 关于如何监管MMPs生产的重要新信息，这些 研究还可能确定治疗药物的新潜在靶点 牙周炎。