ROLE OF EPIDERMAL GROWTH-FACTOR IN INTESTINAL REGENERATION

We have quantitated uptake of radiolabeled recombinant human urogastrone/epidermal growth factor (I-125 rhUG/EGF), crypt cell production rate, and rate of epithelialization on days 2, 4, 8, and 12 after operation in the ileum, mucosa adjacent to the wound, and neomucosa (regenerating mucosa) during healing of a full-thickness ileal defect in rats. The uptake of I-125 rhUG/EGF in adjacent mucosa and neomucosa was highest on the day 2 (0.64% +/- 0.1% and 0.98% +/- 0.14% injected dose/gm I-125 rhUG) and significantly decreased by postoperative day 8. The crypt cell production rate in the adjacent mucosa and neomucosa (23.8 +/- 4.2 and 21.9 +/- 2.1 cells/crypt/hr) peaked on the postoperative days 4 and 8, respectively. The epithelial cell migration rate was increased significantly in the neomucosa on the day 2 (33 +/- 2 mm/day) and tapered gradually until postoperative day 12 (14 +/- 1 mm/day). A linear correlation was evident between the rate of epithelialization and uptake of I-125 rhUG/EGF in the neomucosa (r = 0.93; p less-than-or-equal-to 0.05). These findings suggest that epithelial cell migration occurs earlier than cell proliferation during regeneration of intestinal epithelium and is closely associated with changing concentration of I-125 rhUG/EGF in the neomucosa. This suggests that endogenous EGF may play an important role in intestinal regeneration.