Heparin-binding epidermal growth factor-like growth factor is essential for preservation of gut barrier function after hemorrhagic shock and resuscitation in mice.
BACKGROUND
The aim of the current study was to determine the role of heparin-binding (HB) epidermal growth factor (EGF)-like growth factor as a mediator of gut barrier function after hemorrhagic shock and resuscitation (HS/R) in mice.


METHODS
HS/R was induced in HB-EGF knockout (KO) and wild-type (WT) mice. Intestinal histologic injury scores, intestinal epithelial cell apoptosis, and gut barrier function were determined. Statistical analyses were performed using linear mixed models with P<.05 considered significant.


RESULTS
All mice subjected to HS/R had significantly increased intestinal histologic injury scores, apoptosis indices, and intestinal permeability compared with mice subjected to sham operation. Compared with WT mice, HB-EGF KO mice subjected to HS/R had significantly increased histologic injury (mean injury grade, 4.5 +/- 1 vs 2.75 +/- 0.5 at 3 hours of resuscitation; P<.05), increased apoptosis indices (mean apoptosis index, 6.84 +/- 1.95 vs 3.24 +/- 1.00 at 3 hours of resuscitation; P < .05), and increased mucosal permeability (FD4 clearance 78 +/- 18.91 vs 47.75 +/- 8.06 nL/min/cm(2) at 3 hours of resuscitation; P<.05).


CONCLUSIONS
HB-EGF is essential for the preservation of gut barrier function after HS/R. These findings support the clinical use of HB-EGF in protection of the intestines from disease states associated with intestinal hypoperfusion injury.
Zhang
Hong-Yi
HY
Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH 43205, USA.
Radulescu
Andrei
A
Besner
Gail E
GE
D000818:Animals; D017209:Apoptosis; D020895:Enterocytes / Q000473:pathology; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins