INTESTINAL MUCOSAL GROWTH IN HEALTH & SURGICAL DISEASE

健康的肠粘膜生长

• 批准号: 6740137
• 负责人: Jian-Ying Wang
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740137
• 关键词: cell growth regulation; cell proliferation; gene expression; growth inhibitors; in situ hybridization; intestinal mucosa; laboratory rat; oncoprotein p21; p53 gene /protein; polyamines; tissue /cell culture; transfection

The inhibition of gastrointestinal mucosal growth occurs commonly in critical illness including a variety of surgical conditions. Data from the Investigator's laboratory and others indicate that the supply of polyamines to the dividing cells is an important step in the regulation of normal intestinal mucosal growth and that decreasing cellular polyamines inhibits cell renewal. The goal of this project is to elucidate the fundamental mechanisms by which the intestinal mucosal renewal process is impaired following polyamine depletion. The hypothesis is that inhibition of polyamine synthesis suppresses intestinal mucosal growth by altering expression of the p53 gene. Four specific aims are proposed: 1) to identify the relationship between expression of the p53 gene and growth inhibition in small intestinal mucosa in vivo, 2) to determine the role of cellular polyamines in p53 gene expression in intestinal crypt cells in vitro. The Investigators will first define the level where the effect of polyamines on p53 gene expression occurs and then concentrate on understanding the mechanism by which polyamines modulate post-transcription of the p53 gene, 3) to determine the role of increased p53 gene expression in growth inhibition following polyamine depletion. The Investigators will determine whether decreasing p53 levels by antisense oligonucleotides or increasing p53 levels by transfecting a conditional p53 expression vector alters intestinal epithelial cell growth in the presence or absence of polyamines, 4) to identify the basic mechanism by which p53 results in the growth inhibition following polyamine depletion. The Investigators will elucidate the role of p21cip1/waf1 in p53-mediated inhibition of intestinal epithelial cell proliferation in polyamine-deficient cells. The Investigators propose that these studies will enhance understanding of the biology of intestinal mucosal growth and have broader implications for the pathophysiology of mucosal growth inhibition in critical illness.

胃肠道粘膜生长受到抑制常见 危重疾病，包括各种手术条件。 数据来自 研究人员的实验室和其他人表明，多胺的供应 细胞分裂是调节正常肠道的重要一步 粘膜生长，减少细胞多胺会抑制细胞更新。 该项目的目标是阐明基本机制 多胺后肠粘膜更新过程受损 消耗。 假设抑制多胺合成会抑制 通过改变p53基因的表达来促进肠粘膜生长。 四 提出具体目标：1）识别表达式之间的关系 p53基因的影响和体内小肠粘膜的生长抑制，2) 确定细胞多胺在肠道 p53 基因表达中的作用 体外隐窝细胞。 调查人员将首先定义 多胺对p53基因表达的影响发生，然后集中于 了解多胺调节转录后的机制 p53 基因，3) 确定 p53 基因表达增加在 多胺消耗后的生长抑制。 调查人员将 确定是否通过反义寡核苷酸或 通过转染条件 p53 表达载体增加 p53 水平 在存在或不存在的情况下改变肠上皮细胞的生长 多胺，4) 确定 p53 导致的基本机制 多胺消耗后的生长抑制。 调查人员将 阐明 p21cip1/waf1 在 p53 介导的肠道抑制中的作用 多胺缺陷细胞中的上皮细胞增殖。 调查员 表明这些研究将增强对生物学的理解 肠粘膜生长并对病理生理学具有更广泛的影响 危重疾病中粘膜生长抑制的研究。