EXPRESSION OF EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA AFTER EXPOSURE OF RAT GASTRIC-MUCOSA TO STRESS

Background: This study was designed to determine whether transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and th eir common receptor (EGFR) are involved in the recovery of the gastric mucosa after exposure to water immersion and restraint stress. Method s: Wistar rats were exposed to a standard period (3.5 h) of water imme rsion 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 th e ulcerations was measured planimetrically, half of the stomach was ta ken for measurement of DNA synthesis, and the other half was embedded in paraffin. Sections were stained immunohistochemically for prolifera ting nuclear antigen (an index of cellular proliferation) and TGF-alph a, 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 exp ression of EGF peaked at 4 h, whereas the expression of EGFR peaked 6 h after stress. Thereafter the labelling indices for EGF and EGFR decr eased, whereas DNA synthesis showed a gradual increase starling after about 6 h and peaking 12 h after the stress. In contrast, immunohistoc hemical expression of TGF-alpha showed a constant increase for up to 1 2 h after stress. Cell proliferation reached a maximum after 6 h and r eturned to normal values 12 h after the stress. Conclusions: EFG and T GF-alpha and their receptors are involved in the mucosal recovery from stress, and this is followed by enhanced DNA synthesis and mucosal ce ll proliferation.