MECHANISMS OF INTESTINAL CELL MIGRATION

肠细胞迁移的机制

• 批准号: 6381820
• 负责人: JON Marc RHOADS
• 金额: $ 7.28万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6381820
• 关键词: arginine; biological signal transduction; cell migration; epidermal growth factor; focal adhesion kinase; gastrointestinal epithelium; insulinlike growth factor; nitric oxide; ornithine decarboxylase; platelet derived growth factor; polyamines; protein tyrosine kinase; serum; transforming growth factors

DESCRIPTION (adapted from the application) Currently, the only available treatments for infants with infectious diarrhea are oral rehydration and antibiotics. Previous work focused on amino acids, specifically glutamine (GLN) and arginine (ARG), because of their cost, safety, proabsorptive effect, and capacity to promote intestinal repair. Of the two amino acids, ARG was found to be more effective in enhancing restitution, the initial stage of intestinal repair during which the columnar cells migrate to cover basement membrane. ARG synergized with fetal bovine serum or a bovine serum concentrate to enhance migration of wounded intestinal epithelial monolayers and to facilitate recovery of transepithelial electrical resistance of acutely injured pig ileum. The aims of the current proposal are to study the mechanisms of these complementary effects of ARG and serum. The central hypothesis is that after injury serum (and bovine serum concentrate) provide growth factors which synergize with arginine-derived nitric oxide and polyamines to potentiate molecular signaling during migration and restitution. Focal adhesions are multiprotein complexes in extending lamellipodia during epithelial cell migration. Several kinases are activated by protein tyrosine phosphorylation at focal adhesions during intestinal cell migration. We will measure the expression and activity of focal adhesion kinase (FAK), calcium-dependent tyrosine kinase (CADTK, also called PYK-2), extracellular-related kinases (ERK's -1 and -2), and p70s6k during intestinal cell migration, comparing cells and tissues treated with ARG + serum. Active growth peptides in serum will be identified and quantified. We will determine if ARG potentiates serum growth factor signaling or activates separate signaling pathways during migration.

描述（改编自应用程序） 目前，治疗婴儿感染性腹泻的唯一方法 是口服补液和抗生素。以前的工作重点是氨基酸， 特别是谷氨酰胺 (GLN) 和精氨酸 (ARG)，因为它们的成本、安全性、 促吸收作用和促进肠道修复的能力。两者之中 氨基酸，ARG被发现在增强恢复方面更有效， 肠道修复的初始阶段，在此期间柱状细胞迁移到 覆盖基底膜。 ARG 与胎牛血清或牛血清协同作用 血清浓缩物增强受伤肠上皮的迁移 单层细胞并促进跨上皮电阻的恢复 严重受伤的猪回肠。当前提案的目的是研究 ARG 和血清的这些互补作用的机制。中央 假设是损伤后血清（和牛血清浓缩物）提供 与精氨酸衍生的一氧化氮协同作用的生长因子和 多胺可增强迁移和恢复过程中的分子信号传导。 粘着斑是在片状伪足过程中延伸的多蛋白复合物 上皮细胞迁移。多种激酶被蛋白质酪氨酸激活 肠细胞迁移过程中粘着斑的磷酸化。我们将 测量粘着斑激酶（FAK）的表达和活性， 钙依赖性酪氨酸激酶（CADTK，也称为 PYK-2）， 细胞外相关激酶（ERK's -1 和 -2），以及肠道期间的 p70s6k 细胞迁移，比较用 ARG + 血清处理的细胞和组织。积极的 血清中的生长肽将被鉴定和定量。我们将确定 如果 ARG 增强血清生长因子信号传导或激活单独的 迁移过程中的信号通路。