BACKGROUND: This study was designed to determine whether transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and their common receptor (EGFR) are involved in the recovery of the gastric mucosa after exposure to water immersion and restraint stress. METHODS: Wistar rats were exposed to a standard period (3.5 h) of water immersion and restraint stress. Animals were killed immediately or 2 h, 4 h, 6 h, or 12 h after the stress. Tissues were removed, the area of the ulcerations was measured planimetrically, half of the stomach was taken for measurement of DNA synthesis, and the other half was embedded in paraffin. Sections were stained immunohistochemically for proliferating nuclear antigen (an index of cellular proliferation) and TGF-alpha, EGF, and EGFR. RESULTS: A single stress insult resulted in numerous haemorrhagic erosions in the oxyntic mucosa and a significant drop in DNA synthesis. During the recovery phase a marked increase in the expression of EGF peaked at 4 h, whereas the expression of EGFR peaked 6 h after stress. Thereafter the labelling indices for EGF and EGFR decreased, whereas DNA synthesis showed a gradual increase starting after about 6 h and peaking 12 h after the stress. In contrast, immunohistochemical expression of TGF-alpha showed a constant increase for up to 12 h after stress. Cell proliferation reached a maximum after 6 h and returned to normal values 12 h after the stress. CONCLUSIONS: EFG and TGF-alpha and their receptors are involved in the mucosal recovery from stress, and this is followed by enhanced DNA synthesis and mucosal cell proliferation.
BACKGROUND: This study was designed to determine whether transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and their common receptor (EGFR) are involved in the recovery of the gastric mucosa after exposure to water immersion and restraint stress. METHODS:Wistar rats were exposed to a standard period (3.5 h) of water immersion and restraint stress. Animals were killed immediately or 2 h, 4 h, 6 h, or 12 h after the stress. Tissues were removed, the area of the ulcerations was measured planimetrically, half of the stomach was taken for measurement of DNA synthesis, and the other half was embedded in paraffin. Sections were stained immunohistochemically for proliferating nuclear antigen (an index of cellular proliferation) and TGF-alpha, EGF, and EGFR. RESULTS: A single stress insult resulted in numerous haemorrhagic erosions in the oxyntic mucosa and a significant drop in DNA synthesis. During the recovery phase a marked increase in the expression of EGF peaked at 4 h, whereas the expression of EGFR peaked 6 h after stress. Thereafter the labelling indices for EGF and EGFR decreased, whereas DNA synthesis showed a gradual increase starting after about 6 h and peaking 12 h after the stress. In contrast, immunohistochemical expression of TGF-alpha showed a constant increase for up to 12 h after stress. Cell proliferation reached a maximum after 6 h and returned to normal values 12 h after the stress. CONCLUSIONS: EFG and TGF-alpha and their receptors are involved in the mucosal recovery from stress, and this is followed by enhanced DNA synthesis and mucosal cell proliferation.