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.
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Authors | Chun-Liang Chen, Jixin Yang, Iyore O A James, Hong-Yi Zhang, Gail E Besner |
Journal | Surgery
(Surgery)
Vol. 155
Issue 6
Pg. 1069-80
(Jun 2014)
ISSN: 1532-7361 [Electronic] United States |
PMID | 24856127
(Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 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
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Topics |
- 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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