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

• Published in: Surgery 2014-06, Vol.155 (6), p.1069-1080
• Main Authors: Chen, Chun-Liang, PhD, Yang, Jixin, MD, James, Iyore O.A., MD, Zhang, Hong-yi, MD, Besner, Gail E., MD
• Format: Article
• Language: English
• Subjects: 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; Surgery; Wnt Signaling Pathway - drug effects
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2014.01.013

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.