The role of epidermal growth factor (EGF) and its receptor in mucosal protection, adaptation to injury, and ulcer healing: involvement of EGF-R signal transduction pathways.
Growth factors and their receptors are known to play important roles in normal cell proliferation, morphogenesis, tissue repair, and ulcer healing. Epidermal growth factor (EGF) inhibits acid secretion, exerts a trophic effect on gastroduodenal mucosa, protects gastric mucosa against injury, mediates mucosal adaptation, and accelerates gastroduodenal ulcer healing by stimulating cell migration and proliferation. EGF exerts its actions by binding to its receptor, EGF-R, a transmembrane protein tyrosine kinase, which triggers receptor dimerization, autophosphorylation, and recruitment of kinase substrates. These events result in Ras (GTP-binding protein) activation of the Ras/Raf/MAP kinase pathway, leading to phosphorylation of regulatory proteins and transcription factors and culminating in cell proliferation. Other pathways potentially activated by EGF include the phosphatidylinositol pathway and the JAK/STAT signaling pathway. Recent studies demonstrated that EGF-R-associated tyrosine kinase plays an essential role in regulating gastric mucosal cell proliferation after acute injury and further demonstrated activation of the EGF-R gene, EGF-R phosphorylation, and increased MAP kinase activity during early stages of experimental gastric ulcer healing. Finally, experimental data indicate that Helicobacter pylori vacuolating cytotoxin inhibits healing of experimental gastric ulcers, cell proliferation, binding of EGF to its receptor, EGF-induced EGF-R phosphorylation, and MAP kinase (ERK-2) activation. These H. pylori actions can explain its interference with the ulcer healing process.
Tarnawski
A S
AS
Veterans Administration Medical Center, Long Beach, California 90822, USA.
Jones
M K
MK
D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D005753:Gastric Mucosa / Q000293:injuries* / Q000503:physiopathology*; D016481:Helicobacter Infections / Q000503:physiopathology; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D015398:Signal Transduction; D013276:Stomach Ulcer / Q000503:physiopathology*; D014945:Wound Healing
D004815:Epidermal Growth Factor; D066246:ErbB Receptors