HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR IS CYTOPROTECTIVE FOR INTESTINAL EPITHELIAL-CELLS EXPOSED TO HYPOXIA

Background: During recovery from intestinal ischemic injury, there is rapid growth of intestinal epithelia with regeneration of damaged vill i, This study examines the effects of heparin-binding EGF-like growth factor (HB-EGF) on the recovery of intestinal epithelial cells exposed to hypoxia. Methods: The cytoprotective effects of HB-EGF were analyz ed by placing IEC-18 cells in an anaerobic chamber with various timed HB-EGF treatments (prehypoxia, posthypoxia, pre- and posthypoxia, and no treatment). After 10 hours of hypoxia, lactate dehydrogenase (LDH) release, actin-filament (structural) integrity, adenosine triphosphate (ATP) levels, and posthypoxia proliferative activity were evaluated. Results: LDH analysis showed that HB-EGF exerted a cytoprotective effe ct during hypoxia. Pretreated cells had a significantly lower death ra te during recovery (7.48%) compared with cells with no HB-EGF treatmen t (22.19%, P < .009). Confocal microscopic structural analysis of post hypoxia cells showed that F-actin structure was maintained in treated cells, whereas nontreated cells showed increased structural deteriorat ion. ATP levels were significantly higher in the HB-EGF-treated cells compared with nontreated cells at 48 hours (P < .05). Finally, HB-EGF- treated cells had a significantly improved proliferative ability compa red with nontreated cells during recovery from hypoxia (P <.05). Concl usions: HB-EGF is a mitogenic growth factor for intestinal epithelial cells. Moreover, HB-EGF appears to protect intestinal epithelial cells from hypoxia, in part via maintenance of cytoskeletal structure and A TP stores. Finally, HB-EGF-treated cells also appear to have better pr oliferative abilities during recovery from hypoxia. J Pediatr Surg 33: 973-979. Copyright (C) 1998 by W.B. Saunders Company.