Tarnawski A, Szabo I L, Husain S S, Soreghan B
Gastroenterology Section (111G), VA Medical Center, 5901 E. Seventh Street, Long Beach, CA 90822, USA.
J Physiol Paris. 2001 Jan-Dec;95(1-6):337-44. doi: 10.1016/s0928-4257(01)00046-8.
An ulcer is a deep necrotic lesion penetrating through the entire thickness of the gastrointestinal mucosa and muscularis mucosae. Ulcer healing is a complex and tightly regulated process of filling the mucosal defect with proliferating and migrating epithelial and connective tissue cells. This process includes the re-establishment of the continuous surface epithelial layer, glandular epithelial structures, microvessels and connective tissue within the scar. Epithelial cells in the mucosa of the ulcer margin proliferate and migrate onto the granulation tissue to re-epithelialize the ulcer. Growth factors, such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), trefoil peptides (TP), platelet derived growth factor (PDGF) and other cytokines produced locally by regenerating cells, control re-epithelialization and the reconstruction of glandular structures. These growth factors, most notably EGF, trigger epithelial cell proliferation via signal transduction pathways involving EGF-R- MAP (Erk1/Erk2) kinases. Granulation tissue, which develops at the ulcer base, consists of fibroblasts, macrophages and proliferating endothelial cells, which form microvessels under the control of angiogenic growth factors. These growth factors [bFGF, vascular endothelial growth factor (VEGF) and angiopoietins] promote angiogenesis--capillary vessel formation--thereby allowing for the reconstruction of microvasculature in the mucosal scar, which is essential for delivery of oxygen and nutrients to the healing site. The primary trigger to activate expression of angiogenic growth factors and their receptors appears to be hypoxia. During ulcer healing expression of growth factor genes is tightly regulated in a temporally and spatially ordered manner.
溃疡是一种穿透胃肠道黏膜和黏膜肌层全层的深部坏死性病变。溃疡愈合是一个复杂且受到严格调控的过程，通过增殖和迁移的上皮及结缔组织细胞来填补黏膜缺损。这个过程包括在瘢痕内重新建立连续的表面上皮层、腺上皮结构、微血管和结缔组织。溃疡边缘黏膜中的上皮细胞增殖并迁移到肉芽组织上，使溃疡重新上皮化。生长因子，如表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）、三叶肽（TP）、血小板衍生生长因子（PDGF）以及再生细胞局部产生的其他细胞因子，控制着重新上皮化和腺结构的重建。这些生长因子，尤其是EGF，通过涉及EGF-R-MAP（Erk1/Erk2）激酶的信号转导途径触发上皮细胞增殖。在溃疡底部形成的肉芽组织由成纤维细胞、巨噬细胞和增殖的内皮细胞组成，这些细胞在血管生成生长因子的控制下形成微血管。这些生长因子[bFGF、血管内皮生长因子（VEGF）和血管生成素]促进血管生成——毛细血管形成——从而使黏膜瘢痕中的微血管得以重建，这对于向愈合部位输送氧气和营养物质至关重要。激活血管生成生长因子及其受体表达的主要触发因素似乎是缺氧。在溃疡愈合过程中，生长因子基因的表达在时间和空间上以有序的方式受到严格调控。
