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

Surgery. 2014 Jun;155(6):1069-80. doi: 10.1016/j.surg.2014.01.013. Epub 2014 Feb 6.

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: These data show that HB-EGF preserves Wnt/β-catenin signaling in ISC after I/R injury.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Fluorescent Antibody Technique
  • Heparin-binding EGF-like Growth Factor
  • Ileum / blood supply
  • Ileum / drug effects*
  • Ileum / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Intercellular Signaling Peptides and Proteins / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Random Allocation
  • Receptors, G-Protein-Coupled / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Wnt Signaling Pathway / drug effects*

Substances

  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Lgr5 protein, mouse
  • Protective Agents
  • Receptors, G-Protein-Coupled