REGULATION OF THE STIMULATION OF MUCIN GENE EXPRESSION

粘蛋白基因表达刺激的调节

• 批准号: 6132595
• 负责人: JA SEOK KOO
• 金额: $ 10.27万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-25 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6132595
• 关键词: biological signal transduction; gene expression; interleukin 1; mucins; nuclear receptors; protein biosynthesis; retinoate; retinoid binding proteins

DESCRIPTION (Taken from the Candidate's Abstract) Acute or chronic exposure of environmental insults and toxicants trigger inflammatory pulmonary conditions, resulting in infiltration of inflammatory cells and elevation of inflammatory mediators, and alteration of the integrity and function of the airway epithelium. Hypersecreted visco-elastic mucus causes obstruction of central and peripheral airways in many inflammatory airway diseases such as asthma, cystic fibrosis, chronic bronchitis, and bronchiectasis. Inhibition of over expressed pathophysiologic mucus is one of the major targets for treatments of airway inflammatory disorders. Previously, the candidate has shown that tetinoic acid (RA), a key element required for mucous cell differentiation, mucin production, and mucin gene expression is mediated through retinoic acid receptor alpha. Based on these findings, the candidate hypothesizes that repressing receptor alpha activity will inhibit over expression of mucin gene mRNAs and mucin hypersecretion induced by inflammatory mediators. The specific aims are to clarify: 1) the biochemical mechanisms by which inflammatory mediators increase the expression of mucin gene mRNAs and mucin secretion; 2) the molecular mechanisms by which receptor alpha signaling pathway regulate inflammatory mediators-increased mucin production; and, 3) the molecular mechanisms of a cross-talk between receptor alpha and IL-1 beta signaling pathways.

描述（取自候选人的摘要） 急性或长期暴露环境侮辱和有毒物质触发 炎症性肺部条件，导致炎症浸润 细胞和炎症介体的升高以及完整性的改变 和气道上皮的功能。 分泌的粘弹性粘液 在许多炎症中引起中央和外围气道的阻塞 气道疾病，例如哮喘，囊性纤维化，慢性支气管炎和 支气管扩张。 抑制过度表达的病理生理粘液是 气道炎症性疾病治疗的主要靶标。 以前，候选人已经表明二甲酸（RA）是关键元素 粘液细胞分化，粘蛋白产生和粘蛋白基因所需 表达是通过视黄酸受体α介导的。 基于这些 调查结果，候选人假设抑制受体α活性 将抑制粘蛋白基因mRNA和粘蛋白过度分泌的表达 由炎症介体诱导。 具体目的是澄清：1）生化机制 炎症介质增加了粘蛋白基因mRNA和粘蛋白的表达 分泌; 2）受体α信号传导的分子机制 途径调节炎症介质引起的粘蛋白产生； 3） 受体α和IL-1β之间的串扰的分子机制 信号通路。