Effects of edema on cadherins in small intestine

水肿对小肠钙粘蛋白的影响

• 批准号: 7145711
• 负责人: KAREN S URAY
• 金额: $ 8.23万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 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/7145711
• 关键词: biological signal transduction; cadherins; cell adhesion; cell cell interaction; disease /disorder model; edema; gastrointestinal motility /pressure; gel electrophoresis; hypertension; immunocytochemistry; laboratory rat; muscle contraction; phosphorylation; polymerase chain reaction; protein localization; protein structure function; small intestines; smooth muscle; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Interstitial edema, often associated with abdominal surgery or trauma, has been shown to cause intestinal dysfunction including decreased transit. Thus, intestinal edema development has significant negative impact on the outcome of ICU and post-surgical patients. Preliminary data suggests that edema disrupts signaling by the cell-cell adhesion molecule, cadherin. The general hypothesis is that edema induces tissue remodeling that leads to organ dysfunction. The goal is to investigate the effects of edema at the cellular and molecular level in order to understand the mechanism by which edema induces dysfunction. The specific hypothesis to be addressed in this proposal is that edema disrupts cadherin-mediated cell-cell contacts in intestinal smooth muscle causing a decrease in intestinal transit. The first specific aim is designed to examine the effects of intestinal edema on cadherin signaling in vivo using a venous hypertension rat model. The second specific aim is to correlate changes in cadherin signaling with changes in intestinal contractility in the rat intestinal edema model. In the third specifc aim, an intestinal smooth muscle cell culture model will be used to elucidate the role of cadherins in smooth muscle contraction. The fourth specific aim is designed to determine the mechanisms by which edema induces alterations in cadherins. The candidate will gain expertise in a relatively new area of cell adhesion while pursuing her long term research interests in fluid balance and microvascular research. The sponor and co-sponsors are experts in their respective fields and have proven track records in training young scientists. The research proposal and training plan will help the candidate establish an independent and complementary research program within the Microvascular Research Group. The KO1 award will facilitate the candidate's progression to independence by supporting the research training activities while the proposed research is being completed including mentoring by experts in the fields of intestinal function, smooth muscle biology, and cadherin/catenin signaling, attending research conferences relative to her area of research, and taking grant writing and ethics courses.

描述(由申请人提供)： 间质水肿通常与腹部手术或创伤相关，已被证明会导致肠道功能障碍，包括转运减少。因此，肠水肿的发展对ICU和手术后患者的预后有显著的负面影响。初步数据显示，水肿会通过细胞间黏附分子钙粘附素干扰信号传递。一般的假设是，水肿会引起组织重塑，从而导致器官功能障碍。其目的是在细胞和分子水平上研究水肿胀的影响，以了解水肿胀导致功能障碍的机制。这项建议中要解决的具体假设是，水肿扰乱了钙粘附素介导的肠道平滑肌细胞-细胞接触，导致肠道转运减少。第一个具体目标是利用静脉高压大鼠模型在体内检测肠道水肿对钙粘附素信号的影响。第二个具体目的是在大鼠肠水肿模型中将钙粘附素信号的变化与肠收缩功能的变化联系起来。在第三个特定目标中，将使用肠平滑肌细胞培养模型来阐明钙粘附素在平滑肌收缩中的作用。第四个具体目标是确定浮肿引起钙粘附素改变的机制。候选人将在一个相对较新的细胞黏附领域获得专业知识，同时追求她在流体平衡和微血管研究方面的长期研究兴趣。发起人和共同赞助人都是各自领域的专家，并在培训年轻科学家方面有良好的记录。研究提案和培训计划将帮助候选人在微血管研究组内建立一个独立和补充的研究计划。KO1奖将通过在拟议的研究即将完成时支持研究培训活动来促进候选人的独立发展，包括由肠道功能、平滑肌肉生物学和钙粘连蛋白/连环蛋白信号领域的专家指导，参加与其研究领域相关的研究会议，并参加拨款撰写和伦理课程。