Ets transcription factors in intestinal biology

肠道生物学中的 Ets 转录因子

• 批准号: 7227567
• 负责人: PAUL JEDLICKA
• 金额: $ 13.47万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7227567
• 关键词: Accounting; Adult; Affect; Animals; Binding; Biological; Biological Models; Biological Process; Biology; Cell Communication; Cell Proliferation; Cells; Cessation of life; Chemical Agents; Chromosomes; Colon; Colon Carcinoma; Complex; Condition; Control Animal; Data; Development; Disease; Disruption; Dominant-Negative Mutation; Embryonic Development; Enterocolitis; Environment; Epithelial; Epithelial Neoplasms; Epithelium; Exhibits; Family; Functional disorder; Genetic; Genus Cola; Growth; Human; Impairment; Infection; Inflammation; Inflammatory Bowel Diseases; Injury; Intestinal Neoplasms; Intestines; Investigation; Learning; Life; Maintenance; Malignant Neoplasms; Mediating; Mitolactol; Morphogenesis; Mus; Natural regeneration; Neoplasms; Neoplastic Cell Transformation; Numbers; Nutrient; Organ; Organism; Pathologic; Pathway interactions; Phenotype; Physiological; Play; Pongidae; Premalignant; Process; Protein Family; Protein Overexpression; Proteins; Publishing; RNA; Research Design; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Signal Transduction; Small Intestines; Sodium Dextran Sulfate; Source; Staining method; Stains; Structure; Surface; System; Tetracycline Control; Tissues; Trans-Activators; Transgenes; Transgenic Mice; Tumor Burden; Type I Epithelial Receptor Cell; VP 16; Villus; Woman; absorption; adenoma; base; body system; cell growth; cell motility; design; extracellular; in vivo; intestinal crypt; intestinal epithelium; intestinal villi; malformation; member; men; mouse model; neoplastic; pressure; programs; promoter; response; response to injury; self-renewal; transcription factor; transgene expression; villin

DESCRIPTION (provided by applicant): The intestine is a complex and dynamic organ that, under normal physiologic conditions, performs a number of functions in the organism, some of which, including nutrient absorption, are essential for survival. The intestine is subject to pathologic disturbances in a number of diseases affecting humans, including developmental malformations, inflammatory bowel disease (affecting 1 million people in the US each year), and cancer, including colon cancer (which accounts for 10% of cases of cancer and 10% of deaths from cancer in men and women each in the US each year). Members of the Ets transcription factor family are important regulators of pathways that mediate cell growth, differentiation, and interactions between cells and the surrounding environment. There is evidence that Ets factors are important in the formation and normal function of the intestine, in intestinal injury, such as occurs in inflammatory bowel disease, and in intestinal (colon) cancer. The long-term objectives of the proposed studies are to elucidate how Ets factors impact these processes. We have developed an animal (mouse) model system designed to block or enhance Ets factor function in the developing and adult intestine in the living organism. We now propose to use this model system to characterize how Ets factors regulate the formation and maintenance of the functional unit of the intestine (the so-called "crypt-villus axis") under normal conditions and conditions of intestinal injury, as well as how they regulate the initiation and/or progression of intestinal (colon) cancer. As the studies will be conducted in a mouse model system, in which intestinal structure and function are extremely similar to those in humans, it is expected that the information learned will have direct relevance to the understanding of normal intestinal function and disease, including inflammatory bowel disease and colon cancer, both prevalent diseases causing significant suffering and death, in humans.

描述（由申请人提供）： 肠道是一个复杂而动态的器官，在正常生理条件下，在生物体中执行许多功能，其中一些功能，包括营养吸收，对于生存至关重要。肠道在影响人类的许多疾病中受到病理学干扰，包括发育畸形、炎性肠病（每年影响美国100万人）和癌症，包括结肠癌（每年在美国男性和女性中占癌症病例的10%和癌症死亡的10%）。Ets转录因子家族的成员是介导细胞生长、分化以及细胞与周围环境之间相互作用的途径的重要调节剂。有证据表明，Ets因子在肠的形成和正常功能中、在肠损伤中（例如发生在炎性肠病中）和在肠（结肠）癌中是重要的。拟议的研究的长期目标是阐明Ets因素如何影响这些过程。我们已经开发了一种动物（小鼠）模型系统，旨在阻断或增强Ets因子在生物体发育和成年肠道中的功能。我们现在建议使用该模型系统来表征Ets因子如何在正常条件和肠损伤条件下调节肠功能单元（所谓的“隐窝-绒毛轴”）的形成和维持，以及它们如何调节肠（结肠）癌的起始和/或进展。由于研究将在小鼠模型系统中进行，其中肠道结构和功能与人类极为相似，因此预计所了解的信息将与理解正常肠道功能和疾病直接相关，包括炎症性肠病和结肠癌，这两种疾病都是导致人类严重痛苦和死亡的流行疾病。