Journal
CELLS
Volume 10, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cells10081964
Keywords
gastric ulcer healing; growth factors; signaling pathways; angiogenesis; vasculogenesis; bone marrow derived endothelial progenitor cells
Categories
Funding
- United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Service [I01 BX000626-05A2]
Ask authors/readers for more resources
This article reviews the cellular and molecular mechanisms of gastric ulcer healing, focusing on the processes involving cell dedifferentiation, proliferation, migration, re-epithelialization, angiogenesis, and more, all controlled by growth factors and cytokines. Local therapy with specific growth factors and proteins can accelerate and improve ulcer healing, with future directions including gene and protein therapies, stem cells, and tissue engineering.
In this article we review the cellular and molecular mechanisms of gastric ulcer healing. A gastric ulcer (GU) is a deep defect in the gastric wall penetrating through the entire mucosa and the muscularis mucosae. GU healing is a regeneration process that encompasses cell dedifferentiation, proliferation, migration, re-epithelialization, formation of granulation tissue, angiogenesis, vasculogenesis, interactions between various cells and the matrix, and tissue remodeling, all resulting in scar formation. All these events are controlled by cytokines and growth factors (e.g., EGF, TGF alpha, IGF-1, HGF, bFGF, TGF beta, NGF, VEGF, angiopoietins) and transcription factors activated by tissue injury. These growth factors bind to their receptors and trigger cell proliferation, migration, and survival pathways through Ras, MAPK, PI3K/Akt, PLC-gamma, and Rho/Rac/actin signaling. The triggers for the activation of these growth factors are tissue injury and hypoxia. EGF, its receptor, IGF-1, HGF, and COX-2 are important for epithelial cell proliferation, migration, re-epithelialization, and gastric gland reconstruction. VEGF, angiopoietins, bFGF, and NGF are crucial for blood vessel regeneration in GU scars. The serum response factor (SRF) is essential for VEGF-induced angiogenesis, re-epithelialization, and blood vessel and muscle restoration. Local therapy with cDNA of human recombinant VEGF165 in combination with angiopoietin1, or with the NGF protein, dramatically accelerates GU healing and improves the quality of mucosal restoration within ulcer scars. The future directions for accelerating and improving healing include local gene and protein therapies with growth factors, their combinations, and the use of stem cells and tissue engineering.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available