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Heparin-binding EGF-like growth factor protects pericytes from injury.

AbstractBACKGROUND:
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.
MATERIALS AND 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.
AuthorsXiaoyi Yu, Andrei Radulescu, Chun-Liang Chen, Iyore O James, Gail E Besner
JournalThe Journal of surgical research (J Surg Res) Vol. 172 Issue 1 Pg. 165-76 (Jan 2012) ISSN: 1095-8673 [Electronic] United States
PMID20863525 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Inc. All rights reserved.
Chemical References
  • Hbegf protein, mouse
  • Hbegf protein, rat
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Transforming Growth Factor beta1
Topics
  • Animals
  • Anoxia (physiopathology)
  • Apoptosis (drug effects, physiology)
  • Cell Differentiation (drug effects)
  • Cell Line
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins (pharmacology)
  • Intestines (blood supply)
  • Male
  • Mesoderm (cytology, drug effects)
  • Mice
  • Mice, Inbred C3H
  • Models, Animal
  • Pericytes (cytology, drug effects, physiology)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (pathology, physiopathology, prevention & control)
  • Transforming Growth Factor beta1 (pharmacology)

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