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，唯一可用的治疗感染性腹泻的婴儿 是口服补液和抗生素以前的工作集中在氨基酸， 特别是谷氨酰胺（GLN）和精氨酸（ARG），因为它们成本、安全性 促进吸收作用和促进肠道修复的能力。两 氨基酸，ARG被发现在增强恢复方面更有效， 肠修复的初始阶段，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 增强受伤肠上皮细胞迁移的血清浓缩物 单层并促进跨上皮电阻的恢复 猪回肠的急性损伤目前建议的目的是研究 ARG和血清的这些互补作用的机制。中央 假设是在损伤后血清（和牛血清浓缩物）提供了 生长因子，其与精氨酸衍生的一氧化氮协同作用， 多胺在迁移和恢复过程中增强分子信号传导。 局灶性粘连是多蛋白复合物在延长板状伪足过程中 上皮细胞迁移。几种激酶被蛋白酪氨酸激活 在肠细胞迁移过程中，在粘着斑处的磷酸化。我们将 测定粘着斑激酶（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的-1和-2），和p70 s6 k在肠 细胞迁移，比较用ARG +血清处理的细胞和组织。活性 将鉴定和定量血清中的生长肽。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 迁移过程中的信号传导