MECHANISMS OF INTESTINAL CELL MIGRATION

说明(改编自应用程序) 目前，治疗婴儿感染性腹泻的唯一有效方法 就是口服补液和抗生素。之前的工作主要集中在氨基酸上， 尤其是谷氨酰胺(Gln)和精氨酸(ARG)，因为它们的成本、安全性、 前吸收作用，促进肠道修复的能力。两个中的一个 氨基酸，精氨酸被发现在促进恢复方面更有效， 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。精氨酸与胎牛血清或牛的协同作用 血清浓缩物促进损伤肠上皮细胞迁移 单层和促进跨上皮电阻的恢复 严重受伤的猪回肠。目前建议的目的是研究 ARG和血清的这种互补作用的机制。中环 假设在受伤后血清(和牛血清浓缩物)提供 生长因子与精氨酸源性一氧化氮和 多胺在迁移和恢复过程中增强分子信号。 局灶性粘连是脂膜扩张过程中的多蛋白复合体。 上皮细胞迁移。蛋白酪氨酸激活了几种蛋白激酶 肠道细胞迁移过程中局灶性粘连的磷酸化。我们会 检测粘着斑激酶(FAK)的表达和活性， 钙依赖酪氨酸激酶(CADTK，又称PYK-2)， 细胞外相关蛋白(ERK‘s-1和-2)和p70S6K在肠道中的表达 细胞迁移，比较ARG+血清处理的细胞和组织。主动型 将对血清中的生长肽进行鉴定和定量。我们将决定 如果ARG增强血清生长因子信号或激活单独的 迁移过程中的信号通路。

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.