Heparin-binding EGF-like growth factor promotes intestinal anastomotic healing.
BACKGROUND
We have accumulated multiple lines of evidence supporting the ability of HB-EGF to protect the intestines from injury and to augment the healing of partial-thickness scald burns of the skin. The aim of the current study was to investigate the role of heparin-binding EGF-like growth factor (HB-EGF) in intestinal anastomotic wound healing.


METHODS
HB-EGF (-/-) knockout (KO) mice (n=42) and their HB-EGF (+/+) wild type (WT) counterparts (n=33), as well as HB-EGF transgenic (TG) mice (n=26) and their (WT) counterparts (n=27), underwent division and reanastomosis of the terminal ileum. In addition, WT mice (n=21) that received enteral HB-EGF (800 μg/kg) underwent the same operative procedure. Anastomotic bursting pressure was measured at 3 and 6 d postoperatively. Tissue sections were stained with hematoxylin and eosin to assess anastomotic healing, and Picrosirus red to assess collagen deposition. Immunohistochemistry using anti-von Willebrand factor antibodies was performed to assess angiogenesis. Complications and mortality were also recorded.


RESULTS
HB-EGF KO mice had significantly lower bursting pressures, lower healing scores, higher mortality, and higher complication rates postoperatively compared with WT mice. Collagen deposition and angiogenesis were significantly decreased in KO mice compared with WT mice. Conversely, HB-EGF TG mice had increased anastomotic bursting pressure, higher healing scores, lower mortality, lower complication rates, increased collagen deposition, and increased angiogenesis postoperatively compared with WT mice. WT mice that received HB-EGF had increased bursting pressures compared with non-HB-EGF treated mice.


CONCLUSIONS
Our results demonstrate that HB-EGF is an important factor involved in the healing of intestinal anastomoses.
Radulescu
Andrei
A
Center for Perinatal Research, Department of Pediatric Surgery, The Research Institute at Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.
Zhang
Hong-Yi
HY
Chen
Chun-Liang
CL
Chen
Yan
Y
Zhou
Yu
Y
Yu
Xiaoyi
X
Otabor
Iyore
I
Olson
Jacob K
JK
Besner
Gail E
GE
D000714:Anastomosis, Surgical; D000818:Animals; D003094:Collagen / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D007422:Intestines / Q000473:pathology / Q000502:physiology* / Q000601:surgery*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D011183:Postoperative Complications / Q000401:mortality / Q000503:physiopathology* / Q000517:prevention & control; D011312:Pressure; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D003094:Collagen