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

Abstract

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.

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.

• Authors: Xiaoyi Yu, Andrei Radulescu, Chun-Liang Chen, Iyore O James, Gail E Besner
• Journal: The Journal of surgical research (J Surg Res) Vol. 172 Issue 1 Pg. 165-76 (Jan 2012) ISSN: 1095-8673 [Electronic] United States
• PMID: 20863525 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 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
• Apoptosis (drug effects, physiology)
• Cell Differentiation (drug effects)
• Cell Line
• Cell Proliferation (drug effects)
• Cells, Cultured
• Heparin-binding EGF-like Growth Factor
• Hypoxia (physiopathology)
• 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)