The Critical Role of Growth Factors in Gastric Ulcer Healing: The Cellular and Molecular Mechanisms and Potential Clinical Implications.

Abstract

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, TGFα, IGF-1, HGF, bFGF, TGFβ, 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-γ, 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: Andrzej S Tarnawski, Amrita Ahluwalia
• Journal: Cells (Cells) Vol. 10 Issue 8 (08 02 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34440733 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Review)

Chemical References

• Cytokines
• Intercellular Signaling Peptides and Proteins
• Transcription Factors
• Insulin-Like Growth Factor I
• Nerve Growth Factor

Topics

• Animals
• Cytokines (metabolism)
• Humans
• Insulin-Like Growth Factor I (therapeutic use)
• Intercellular Signaling Peptides and Proteins (metabolism, therapeutic use)
• Neovascularization, Physiologic
• Nerve Growth Factor (metabolism, therapeutic use)
• Signal Transduction (genetics)
• Stomach Ulcer (drug therapy, metabolism, pathology)
• Transcription Factors (metabolism)