Growth factors and their receptors play important roles in cell proliferation, migration, tissue injury repair and
ulcer healing. In gastric mucosa,
transforming growth factor alpha (
TGF-alpha) and
epidermal growth factor (
EGF) by activating their common receptor, control cell proliferation.
TGF-alpha predominantly plays this role under normal conditions and after acute injury, while
EGF exerts its actions mainly during healing of chronic
ulcers. During regeneration of injured gastric mucosa, these
growth factors serve predominantly to restore the epithelial component. Other
growth factors,
basic fibroblast growth factor (bFGF) and
vascular endothelial growth factor (
VEGF) serve to promote restoration of the connective tissue and microvessels (angiogenesis) in injured mucosa. During healing of chronic
ulcers, a new epithelial lineage secreting
EGF and other growth
peptides develops and the majority of cells lining the
ulcer margin overexpress the
EGF receptor. Activation of the
EGF receptor induces dramatic increases in MAP (Erk -1 and -2)
kinase activity and phosphorylation levels. Inhibition of this signaling pathway dramatically delays
ulcer healing. Granulation connective tissue, which grows under the stimulation of bFGF and
VEGF is the major source for regeneration of connective tissue lamina propria and microvessels within the
ulcer scar. Other
growth factors such as
insulin - like growth factor,
keratinocyte growth factor,
hepatocyte growth factor and
trefoil peptides have been implicated in gastrointestinal (
gastric ulcers,
colitis) regeneration following injury. This paper is intended to provide an overview of the role of
growth factors in gastrointestinal mucosal regeneration.