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 villi. 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 analyzed 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 effect during hypoxia. Pretreated cells had a significantly lower death rate during recovery (7.48%) compared with cells with no HB-EGF treatment (22.19%, P < .009). Confocal microscopic structural analysis of posthypoxia cells showed that F-actin structure was maintained in treated cells, whereas nontreated cells showed increased structural deterioration. 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 compared with nontreated cells during recovery from hypoxia (P < .05).
CONCLUSIONS: 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 ATP stores. Finally, HB-EGF-treated cells also appear to have better proliferative abilities during recovery from hypoxia.