Upregulation of endogenous heparin-binding EGF-like growth factor (HB-EGF) expression after intestinal ischemia/reperfusion injury.
Expression of endogenous heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a proven intestinal cytoprotective molecule, was examined in intestinal epithelial cells (IEC) in vitro, and in intestine undergoing ischemia/reperfusion (I/R) injury in vivo. In vitro, cells were exposed to anoxia for 90 min followed by reoxygenation for 1-3 h (A/R). In vivo, total midgut I/R injury was produced in rats by occlusion of the superior mesenteric artery for 30 or 90 min followed by reperfusion for 4 h. In situ hybridization and immunohistochemistry were used to study HB-EGF mRNA expression and protein production. In vitro, normal IEC had no detectable HB-EGF mRNA or protein expression. After anoxia, cells expressed HB-EGF mRNA and protein, with expression reaching a peak 2-3 h after reoxygenation. In vivo, only very low levels of HB-EGF mRNA and no detectable protein were found in normal intestine. Four hours after I/R, HB-EGF protein was detected in villous epithelia subjected to 30 min but not 90 min of ischemia, whereas HB-EGF mRNA was highly expressed after both ischemic intervals. Endogenous HB-EGF is immediately upregulated in IEC after A/R injury and in intestine after I/R injury. Thus, HB-EGF acts as an immediate early gene under these conditions.
Department of Pediatric Surgery, Children's Hospital, and Ohio State University College of Medicine and Public Health, Columbus, Ohio, USA.
Guliang
G
Xia
Amy W
AW
Rachfal
Abigail E
AE
Martin
Gail E
GE
Besner
D000818:Animals; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000293:injuries*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor