Heparin-binding epidermal growth factor-like growth factor restores Wnt/β-catenin signaling in intestinal stem cells exposed to ischemia/reperfusion injury.

We have previously demonstrated that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) protects the intestines from injury in several different experimental animal models. In the current study, we investigated whether the ability of HB-EGF to protect the intestines from ischemia/reperfusion (I/R) injury was related to its effects on Wnt/β-catenin signaling in intestinal stem cells (ISC).
Lucien-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-enhanced green fluorescent protein (EGFP) transgenic (TG) mice with fluorescently labeled ISC, as well as the same mice treated with intraluminal HB-EGF or genetically engineered to overexpress HB-EGF, were exposed to segmental mesenteric artery occlusion (sMAO) to the terminal ilium. Wnt/β-catenin signaling was evaluated using immunofluorescent staining and Western blotting.
LGR5 expression and Wnt/β-catenin signaling in the ISC of the terminal ilium of LGR5-EGFP TG mice was significantly reduced 24 hours after sMAO. Intraluminal administration of HB-EGF or HB-EGF overexpression in these mice led to preservation of LGR5 expression and Wnt/β-catenin signaling.
These data show that HB-EGF preserves Wnt/β-catenin signaling in ISC after I/R injury.
AuthorsChun-Liang Chen, Jixin Yang, Iyore O A James, Hong-Yi Zhang, Gail E Besner
JournalSurgery (Surgery) Vol. 155 Issue 6 Pg. 1069-80 (Jun 2014) ISSN: 1532-7361 [Electronic] United States
PMID24856127 (Publication Type: Evaluation Studies, Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014 Mosby, Inc. All rights reserved.
Chemical References
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Lgr5 protein, mouse
  • Protective Agents
  • Receptors, G-Protein-Coupled
  • Animals
  • Blotting, Western
  • Fluorescent Antibody Technique
  • Heparin-binding EGF-like Growth Factor
  • Ileum (blood supply, drug effects, metabolism)
  • Intercellular Signaling Peptides and Proteins (pharmacology, therapeutic use)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protective Agents (pharmacology, therapeutic use)
  • Random Allocation
  • Receptors, G-Protein-Coupled (metabolism)
  • Reperfusion Injury (drug therapy, metabolism)
  • Stem Cells (drug effects, metabolism)
  • Wnt Signaling Pathway (drug effects)

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