Heparin-binding EGF-like growth factor protects pericytes from injury.
BACKGROUND
We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes angiogenesis and preserves mesenteric microvascular blood flow in several models of intestinal injury. The current study was designed to evaluate the effect of HB-EGF on pericytes, since these cells function to regulate capillary blood flow and new capillary growth.


METHODS
C3H/10T1/2 mouse mesenchymal cells were differentiated into pericyte-like cells in vitro using transforming growth factor-β1 (TGF-β1). In addition, primary pericyte cultures were established from rat brain. The effect of HB-EGF on pericyte proliferation was assessed. In addition, cells were stressed by exposure to anoxia, and apoptosis determined. In vivo, we examined the effect of HB-EGF on pericytes in a model of intestinal I/R injury based on superior mesenteric artery occlusion (SMAO) in mice.


RESULTS
Differentiated C3H/10T1/2 cells (pericyte-like cells) demonstrated morphologic characteristics of pericytes, and expressed pericyte specific markers. Addition of HB-EGF led to significant cell proliferation in differentiated pericyte-like cells, even under conditions of anoxic stress. Addition of the EGF receptor inhibitor AG 1478 led to complete inhibition of the proliferative effects of HB-EGF on pericyte-like cells. In addition, HB-EGF protected pericyte-like cells from anoxia-induced apoptosis. In addition, HB-EGF promoted cell proliferation in primary pericyte cultures. In vivo, administration of HB-EGF to mice subjected to intestinal I/R injury led to protection of pericytes from injury.


CONCLUSIONS
These results suggest that HB-EGF may function as a microcirculatory blood flow regulator, at least in part, via its effects on pericytes.
Yu
Xiaoyi
X
Department of Pediatric Surgery, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Radulescu
Andrei
A
Chen
Chun-Liang
CL
James
Iyore O
IO
Besner
Gail E
GE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D066257:Heparin-binding EGF-like Growth Factor; D000860:Hypoxia / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D020286:Pericytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D053773:Transforming Growth Factor beta1