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.
Department of Surgery, The Ohio State University and Columbus Children's Hospital, 43205, USA.
S B
SB
Pillai
M A
MA
Turman
G E
GE
Besner
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D016923:Cell Death; D015687:Cell Hypoxia; D002460:Cell Line; D019610:Cytoprotection; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology
D000199:Actins; D005456:Fluorescent Dyes; D008934:Mitogens; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase