Surgery
2014 ; 155
(6
): 1069-80
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Heparin-binding epidermal growth factor-like growth factor restores Wnt/?-catenin
signaling in intestinal stem cells exposed to ischemia/reperfusion injury
#MMPMID24856127
Chen CL
; Yang J
; James IO
; Zhang HY
; Besner GE
Surgery
2014[Jun]; 155
(6
): 1069-80
PMID24856127
show ga
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/?-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/?-catenin signaling was evaluated using immunofluorescent staining and
Western blotting. RESULTS: LGR5 expression and Wnt/?-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/?-catenin signaling.
CONCLUSION: These data show that HB-EGF preserves Wnt/?-catenin signaling in ISC
after I/R injury.