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

Chun-liang Chen, Jixin Yang, Iyore O A James, Hong Yi Zhang, Gail E. Besner

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1069-1080
Number of pages12
JournalSurgery (United States)
Volume155
Issue number6
DOIs
StatePublished - 2014

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Catenins
Reperfusion Injury
Epidermal Growth Factor
Heparin
Intercellular Signaling Peptides and Proteins
Stem Cells
Ilium
Mesenteric Arteries
Transgenic Mice
Intestines
G-Protein-Coupled Receptors
Animal Models
Western Blotting
Staining and Labeling
Wounds and Injuries

ASJC Scopus subject areas

  • Surgery

Cite this

Heparin-binding epidermal growth factor-like growth factor restores Wnt/β-catenin signaling in intestinal stem cells exposed to ischemia/reperfusion injury. / Chen, Chun-liang; Yang, Jixin; James, Iyore O A; Zhang, Hong Yi; Besner, Gail E.

In: Surgery (United States), Vol. 155, No. 6, 2014, p. 1069-1080.

Research output: Contribution to journalArticle

Chen, Chun-liang ; Yang, Jixin ; James, Iyore O A ; Zhang, Hong Yi ; Besner, Gail E. / Heparin-binding epidermal growth factor-like growth factor restores Wnt/β-catenin signaling in intestinal stem cells exposed to ischemia/reperfusion injury. In: Surgery (United States). 2014 ; Vol. 155, No. 6. pp. 1069-1080.
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N2 - 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.

AB - 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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