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

Xiaoyi Yu, Andrei Radulescu, Chun Liang Chen, Iyore O. James, Gail E. Besner

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)165-176
Number of pages12
JournalJournal of Surgical Research
Volume172
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • heparin-binding EGF-like growth factor
  • intestine
  • ischemia/reperfusion injury
  • microvasculature
  • pericytes
  • transforming growth factor-β1

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'Heparin-binding EGF-like growth factor protects pericytes from injury'. Together they form a unique fingerprint.

Cite this